Peter Steerenberg - Academia.edu (original) (raw)
Papers by Peter Steerenberg
British journal of cancer, 1996
This paper deals with the utility of immunoliposomes for the delivery of doxorubicin (DXR) to hum... more This paper deals with the utility of immunoliposomes for the delivery of doxorubicin (DXR) to human ovarian carcinoma cells in vitro and in vivo. We aimed to investigate whether immunoliposome-mediated targeting of DXR to ovarian cancer cells translates in an enhanced anti-tumour effect compared with that of non-targeted DXR liposomes (lacking the specific antibody). Target cell binding and anti-tumour activity of DXR immunoliposomes were studied in vitro and in vivo (xenograft model of ovarian carcinoma). In vitro we observed that target cell binding and cell growth inhibition of DXR immunoliposomes is superior to that of non-targeted DXR-liposomes. However, in vivo, despite the efficient target cell binding and good anti-tumour response of DXR-immunoliposomes, no difference in anti-tumour effect, compared with non-targeted DXR-liposomes, could be determined. The results indicate that premature DXR leakage from immunoliposomes occurring before the actual target cell binding and sub...
Journal of Drug Targeting, Feb 1, 1996
Methods in molecular biology (Clifton, N.J.), 2004
Assessment of the value of exhaled NO (eNO) is an attractive tool for studying pulmonary disease,... more Assessment of the value of exhaled NO (eNO) is an attractive tool for studying pulmonary disease, considering its wide advantages (i.e., fast analysis, noninvasive sampling, ability to measure large numbers of subjects [including children], and inexpensive in use). Increased concentrations of eNO have been observed in asthmatic patients' airway infections, allergic rhinitis, and bronchiectasis. During inflammation, specific and nonspecific stimuli elicit expression and de novo synthesis of inducible nitric oxide (iNOS). Once generated in the bronchiolar cells, NO is released from the tissue and diffuses to the lumen of the bronchiolis. Of the two sampling ways (on-line and off-line), the off-line method is suitable for monitoring environmental health effects of air pollution and for obtaining an impression of the prevalence of atopy in epidemiological surveys. For this off-line measurement, a balloon method is developed (sampling exhaled air at location) that includes a sample d...
International archives of occupational and environmental health, 2003
This study investigates the upper and lower inflammatory response induced by natural exposure to ... more This study investigates the upper and lower inflammatory response induced by natural exposure to grass pollen in atopic and non-atopic children. After children's atopic profile had been assessed, their nasal lavage fluid (NAL) and exhaled air was sampled once before and once during the pollen season. Level of nitric oxide (NO) was determined in exhaled air, and the following mediators were measured in NAL: ECP, IL-6, IL-8, albumin, uric acid, and urea. The number of eosinophils in NAL was determined after Giemsa staining. During the experiment ozone and pollen levels were measured continuously. During the pollen season the level of grass pollen was 95 pollen grains per cubic metre. At baseline, 8.0% and 5.4% of total cells in NAL of children sensitive to, respectively, house dust mite (HDM) and pollen + HDM were eosinophils, whereas virtually no eosinophils were observed in NAL of non-atopic children. In contrast to the non-atopic and HDM groups, in children sensitive only to gr...
British journal of cancer, 1982
Virchows Archiv. B, Cell pathology including molecular pathology, 1986
The histology of immunologically mediated tumor regression was studied in the syngenic strain 2 g... more The histology of immunologically mediated tumor regression was studied in the syngenic strain 2 guinea pig/line 10 hepatocellular carcinoma tumor system. Tumor regression was induced non-specifically by the intralesional injection of living Bacillus Calmette-Guérin (BCG) in 7-day-old established tumors (diameter 8-10 mm). In untreated line 10 tumors at day 7 a mild to moderate inflammatory reaction was present, which consisted mainly of small mononuclear cells; in addition large mononuclear cells and basophils were present. Intratumoral BCG-treatment induced a prominent increase in the inflammatory reaction due to an influx of small and large mononuclear cells and neutrophils. Small mononuclear cells were identified mainly as lymphocytes whereas large mononuclear cells belonged mainly to the macrophage line. Intratumoral administration of BCG resulted in a granulomatous reaction. A time-related decrease in the number of tumor cells and an increase in inflammation, associated with pu...
Clinical Immunology and Immunopathology, 1980
Congenitally athymic (mu/mu) rats and their thymus-bearing littermates (+/mu) were obtained by ma... more Congenitally athymic (mu/mu) rats and their thymus-bearing littermates (+/mu) were obtained by mating homozygous males with heterozygous females. In the nude rat, blood lymphocyte counts decreased with age, whereas the number of neutrophils, eosinophils, and monocytes were markedly increased. Serum IgM levels of nude rats were within the normal range of heterozygous littermates, while an age-related reduction was found in the level of IgG. Functional assessment of the cell-mediated immunity indicated the absence of a delayed hypersensitivity to tuberculin, whereas skin allografts were not rejected after 13 weeks. Using the sensitive enzyme-linked immunosorbent assay, IgM and IgG antibodies were not detected against the thymus-dependent antigens tetanus toxoid and ovalbumin. In contrast, no significant reduction occurred in the IgM response of nude rats against the thymus-independent antigen LPS, when compared with heterozygous littermates. Lymphocyte transformation studies with spleen cells showed no response against the mitogens phytohemagglutinin, concanavalin A, and pokeweed, whereas a normal response was seen with LPS. These studies indicate that the nude rat has absent T-cell function.
Toxicology Letters, 2006
Pesticides are designed to interfere with living species, and are inevitably characterized by var... more Pesticides are designed to interfere with living species, and are inevitably characterized by variable levels of toxicity. A number of data is at present available suggesting that the immune system may be a target of the toxic effect of pesticides.
Virchows Archiv B Cell Pathology Including Molecular Pathology, 1988
Virus Research, 1995
The helper T-cell response to the E7 protein of human papillomavirus type 16 (HPV16) was studied ... more The helper T-cell response to the E7 protein of human papillomavirus type 16 (HPV16) was studied using BALB/c (H-2d) mice. Twenty-two overlapping synthetic peptides spanning the HPV16 E7 protein were split into 6 groups. Mice were sensitized using mixtures of synthetic peptides corresponding to each of the groups. Lymph node cell suspensions were cultured with the corresponding mixture of synthetic peptides that was used for sensitization. Two mixtures induced a proliferative response. Analysis of the individual peptides from these mixtures showed that two (overlapping) peptides induced a proliferative response. This response was mediated by CD4+ cells. The common region of the two peptides was found to be a single epitope, and a minimal epitope was demonstrated (AHYNIVTFCCK). In conclusion, in contrast to others, we demonstrated a helper T-cell response in BALB/c mice. This may be due to the fact that we used synthetic peptides as immunizing agent. The helper T-cell epitopes in HPV16 E7 demonstrated previously are partly overlapping with the (minimal) epitope demonstrated here, underlining the 'public' nature of the epitope.
Veterinary Immunology and Immunopathology, 1994
In many human clinical trials and in various animal tumor models, the antitumor effect of high do... more In many human clinical trials and in various animal tumor models, the antitumor effect of high doses of systemically applied interleukin-2 (IL-2) is tested. Our studies focused on the effects of low doses of locally injected IL-2. In this paper, the effect of local injection of low doses of IL-2, i.e. a total dose of 25,000-50,000 units, into papillomas or carcinomas of the bovine vulva is described. In 19 out of 23 (83%) cows treated with IL-2 an effect on the tumor load was observed; in three of these animals, complete regression was obtained. In the majority of cases, regression was not restricted to the tumors injected with IL-2.
Toxicology Letters, 1996
The acute effects of the inhalation of air polluting agents have been examined by many research g... more The acute effects of the inhalation of air polluting agents have been examined by many research groups in both animal models and human beings. For instance, it is evident that exposure to ozone has toxic effects and can lead to lung function disturbances. For this reason it is likely that individuals suffering from COPD or asthma are groups especially at risk with'respect to the effects of ozone. The majority of studies dealing with effects of air pollutants on pulmonary allergy are restricted to IgE mediated allergy (type I allergy). Again for ozone, in animal models for type I allergy it has been demonstrated that exposure can affect the induction as well as the effector phase of this type of hyperimmune reaction (e.g. allergic asthma). Recently it has been demonstrated in animal models that non-IgE mediated 'asthma' T cells, and notably Thl cells, may play a crucial role. In a murine mode1 it was demonstrated that low molecular weight compounds can induce delayed type hypersensitivity-like reactions in the respiratory tract, and that these reactions are associated with the induction of airway hyperreactivity. Such compounds include toluene diisocyanate (TDI), to which immune responses can be readily mounted, and which can cause occupational asthma through its sensitizing capability, but to which IgE is only detected in a minority of patients suffering from TDI-associated asthma. Effects of air pollutants on Thl responses in the respiratory tract have not been studied so far. We have demonstrated that ozone can inhibit resistance to a an intratracheal challenge with Listeriu monocytogenes, indicating suppression of Thl immune responses. In addition, we have shown that ozone exposure suppresses pulmonary delayed type hypersensitivity induced by small molecular weight compounds, as well as the trachea1 hyperreactivity that is induced during the development of these immune responses, again supporting the hypothesis of suppression of Thl responses by ozone exposure. These phenomena may be due to activation of Th2 cell dependent reactions that in turn lead to a downregulation of TM mediated immunity, or to a direct effect on Thl cells or other cell types that are crucial for delayed type hypersensitivity and related airway hyperresponsiveness in this model. These data indicate that exposure to air pollutants may have differential consequences on different types of immune responses in the respiratory tract.
Toxicology Letters, 1995
This paper introduces approaches to tests for potential immunotoxicity in rodents and man and the... more This paper introduces approaches to tests for potential immunotoxicity in rodents and man and the application for evaluation of risk. Chemicals can affect the immune system. Direct effects of chemicals can result in malfunctioning of the system that can lead to decreased resistance to infections or tumors. Auto-immunity, a situation in which immune reactions to self components occur, can also be due to chemicals. Finally, chemicals can induce immune responses causing more harm to the tissue in which they take place than the chemical itself would have done. This situation is called allergy or hypersensitivity. Assessment of potential immunotoxicity can be performed in experimental animals. An array of in vivo assays of the immune system, in addition to ex vivo/in vitro assays are available to study the functional consequences of such immunotoxic effects. In particular host resistance models are valuable in this respect, since they offer endpoints that are relevant for estimation of risk to man. There is a number of examples of immunotoxic compounds. Data on direct immunotoxicity of chemicals are mainly derived from animal research, whereas detailed information in man is available only to a limited extent. The majority of such data comes from immunotherapeutic drugs, intentionally designed to influence the immune system. Environmental pollutants that are reported to have immunotoxic effects include among others dioxin and polychlorinated biphenyls oxidant gases. It is difficult at present to conclude from immunotoxic effects as they have been observed in man what their consequences are in terms of resistance to infections. Assessment of immunotoxic processes in man is difficult, as often detailed information is lacking and the immune system can only be studied to a limited extent. Although tests are available to study immune responses in man, it is often not easy to link the outcome of such assays to exposure to immunotoxicants. Few biomarkers for the immune system exist that provide specific information on the toxic activity in man and extent of exposure, or (susceptibility for) disease associated with chemical exposure.
Photochemistry and Photobiology, 1997
We analyzed natural killer (NK) cell activity in the hairless albino Skh/HR1 mouse, to study whet... more We analyzed natural killer (NK) cell activity in the hairless albino Skh/HR1 mouse, to study whether the NK cell activity plays a role during UV radiation (UVR)-induced carcinogenesis. In 4 h 51Cr-release assays, spleen lymphocytes of specific pathogen-free (spf) Skh/HR1 mice displayed 5-10% spontaneous NK cell activity. This was comparable to NK cell activity in C57B1/6, C3H and athymic NMRI nu/nu mice, which were also kept under spf conditions. In all strains investigated, the low spontaneous NK cell activity could be increased up to 20-30% by intraperitoneal administration of polyinosinic:polycytidylic acid (polyI:C), a standardized in vivo NK cell induction method. The polyI:C potentiation of NK cells in Skh/HR1 mice was similar to that in C57B1/6 and NMRI, but significantly less than in C3H mice. Chronic daily UV irradiation according to a protocol that was also used for induction of carcinogenesis (11-12 weeks, 95 mJ/cm2 of UV exposure from FS40 sunlamps) did not decrease NK cell activity on a cell for cell basis. Neither was the inducibility of NK spleen cell activity with polyI:C in Skh/HR1 mice during UV exposure reduced. Based on total organ basis, the pooled lymph node cells (axillary, mandibulary and inguinal lymph node) showed a doubling of NK cell activity (P < 0.001), mainly due to an almost 100% increase in the number of lymph node cells. In conclusion, UVR does not suppress the normal or inducible NK cell activity at the time of clinical appearance of skin tumors. This suggests that such suppression of NK cell activity is not likely to contribute to UVR-induced carcinogenesis in the Skh/HR1 strain.
Photochemistry and Photobiology, 1998
In this study we investigated the effect of the dietary ingredients fruit and vegetable, green te... more In this study we investigated the effect of the dietary ingredients fruit and vegetable, green tea phenol extract (GTP) and the specific flavonoid components quercetin and chrysin on the UV-induced suppression of the contact hypersensitivity (CHS) response to picryl chloride (PCl). The SKH-1 mice were fed with test diet from 2 or 4 weeks before and during the UV irradiation (daily, 95 mJ/cm2) and tested for the CHS ear-swelling response 10 weeks after the onset of the irradiation. For the CHS, mice were immunized with PCl by epicutaneous application on nonirradiated sites. Four days after sensitization all mice were challenged on both sides of each ear by topical application of one drop PCl. In addition, from mice fed with the fruit and vegetable mixture the number of Langerhans cells (LC) were scored in the skin and from mice fed with quercetin, quercetin levels in plasma were measured at week 11 after the start of UV irradiation. It was found that fruit and vegetable (19% in the diet), GTP (0.1% and 0.01% in the drinking water), quercetin (1% in the diet) and chrysin (1% and 0.1% in the diet), prevented statistically significantly the UV-induced suppression of CHS to PCl. In the skin of mice fed with fruit and vegetables combined with UV irradiation the number of LC were comparable to the control mice, whereas the number of LC were significantly diminished in mice treated with UV only. This protective effect on the presence of LC in the epidermis after UV irradiation, which was also observed in a previous study with quercetin, may play a role in the prevention of UV-induced immunosuppression by the flavonoids tested. In conclusion, we found protection of flavonoids against UV-induced effects on CHS, which may be a common feature of most flavonoids.
Photochemistry and Photobiology, 1997
ABSTRACT
Pediatric Allergy and Immunology, 2003
Nitric Oxide, 1999
Levels of exhaled nitric oxide (NO) were determined in well-characterized atopic and nonatopic su... more Levels of exhaled nitric oxide (NO) were determined in well-characterized atopic and nonatopic subjects on 4 days with a different level of outdoor air pollution. The two groups matched well regarding spirometric values, i.e., no difference with regard to FEV 1 , FVC, and peak flow. On the 4 test days asymptomatic atopic subjects exhaled 1.5-to 2.4-fold higher levels of NO compared with nonatopic subjects. In both groups the increase in exhaled NO in response to air pollution was similar (2.5 times maximal increase, P < 0.01). In conclusion, atopic subjects exhale higher levels of NO compared with nonatopic subjects, but respond to a similar degree to increased levels of air pollution.
British journal of cancer, 1996
This paper deals with the utility of immunoliposomes for the delivery of doxorubicin (DXR) to hum... more This paper deals with the utility of immunoliposomes for the delivery of doxorubicin (DXR) to human ovarian carcinoma cells in vitro and in vivo. We aimed to investigate whether immunoliposome-mediated targeting of DXR to ovarian cancer cells translates in an enhanced anti-tumour effect compared with that of non-targeted DXR liposomes (lacking the specific antibody). Target cell binding and anti-tumour activity of DXR immunoliposomes were studied in vitro and in vivo (xenograft model of ovarian carcinoma). In vitro we observed that target cell binding and cell growth inhibition of DXR immunoliposomes is superior to that of non-targeted DXR-liposomes. However, in vivo, despite the efficient target cell binding and good anti-tumour response of DXR-immunoliposomes, no difference in anti-tumour effect, compared with non-targeted DXR-liposomes, could be determined. The results indicate that premature DXR leakage from immunoliposomes occurring before the actual target cell binding and sub...
Journal of Drug Targeting, Feb 1, 1996
Methods in molecular biology (Clifton, N.J.), 2004
Assessment of the value of exhaled NO (eNO) is an attractive tool for studying pulmonary disease,... more Assessment of the value of exhaled NO (eNO) is an attractive tool for studying pulmonary disease, considering its wide advantages (i.e., fast analysis, noninvasive sampling, ability to measure large numbers of subjects [including children], and inexpensive in use). Increased concentrations of eNO have been observed in asthmatic patients' airway infections, allergic rhinitis, and bronchiectasis. During inflammation, specific and nonspecific stimuli elicit expression and de novo synthesis of inducible nitric oxide (iNOS). Once generated in the bronchiolar cells, NO is released from the tissue and diffuses to the lumen of the bronchiolis. Of the two sampling ways (on-line and off-line), the off-line method is suitable for monitoring environmental health effects of air pollution and for obtaining an impression of the prevalence of atopy in epidemiological surveys. For this off-line measurement, a balloon method is developed (sampling exhaled air at location) that includes a sample d...
International archives of occupational and environmental health, 2003
This study investigates the upper and lower inflammatory response induced by natural exposure to ... more This study investigates the upper and lower inflammatory response induced by natural exposure to grass pollen in atopic and non-atopic children. After children's atopic profile had been assessed, their nasal lavage fluid (NAL) and exhaled air was sampled once before and once during the pollen season. Level of nitric oxide (NO) was determined in exhaled air, and the following mediators were measured in NAL: ECP, IL-6, IL-8, albumin, uric acid, and urea. The number of eosinophils in NAL was determined after Giemsa staining. During the experiment ozone and pollen levels were measured continuously. During the pollen season the level of grass pollen was 95 pollen grains per cubic metre. At baseline, 8.0% and 5.4% of total cells in NAL of children sensitive to, respectively, house dust mite (HDM) and pollen + HDM were eosinophils, whereas virtually no eosinophils were observed in NAL of non-atopic children. In contrast to the non-atopic and HDM groups, in children sensitive only to gr...
British journal of cancer, 1982
Virchows Archiv. B, Cell pathology including molecular pathology, 1986
The histology of immunologically mediated tumor regression was studied in the syngenic strain 2 g... more The histology of immunologically mediated tumor regression was studied in the syngenic strain 2 guinea pig/line 10 hepatocellular carcinoma tumor system. Tumor regression was induced non-specifically by the intralesional injection of living Bacillus Calmette-Guérin (BCG) in 7-day-old established tumors (diameter 8-10 mm). In untreated line 10 tumors at day 7 a mild to moderate inflammatory reaction was present, which consisted mainly of small mononuclear cells; in addition large mononuclear cells and basophils were present. Intratumoral BCG-treatment induced a prominent increase in the inflammatory reaction due to an influx of small and large mononuclear cells and neutrophils. Small mononuclear cells were identified mainly as lymphocytes whereas large mononuclear cells belonged mainly to the macrophage line. Intratumoral administration of BCG resulted in a granulomatous reaction. A time-related decrease in the number of tumor cells and an increase in inflammation, associated with pu...
Clinical Immunology and Immunopathology, 1980
Congenitally athymic (mu/mu) rats and their thymus-bearing littermates (+/mu) were obtained by ma... more Congenitally athymic (mu/mu) rats and their thymus-bearing littermates (+/mu) were obtained by mating homozygous males with heterozygous females. In the nude rat, blood lymphocyte counts decreased with age, whereas the number of neutrophils, eosinophils, and monocytes were markedly increased. Serum IgM levels of nude rats were within the normal range of heterozygous littermates, while an age-related reduction was found in the level of IgG. Functional assessment of the cell-mediated immunity indicated the absence of a delayed hypersensitivity to tuberculin, whereas skin allografts were not rejected after 13 weeks. Using the sensitive enzyme-linked immunosorbent assay, IgM and IgG antibodies were not detected against the thymus-dependent antigens tetanus toxoid and ovalbumin. In contrast, no significant reduction occurred in the IgM response of nude rats against the thymus-independent antigen LPS, when compared with heterozygous littermates. Lymphocyte transformation studies with spleen cells showed no response against the mitogens phytohemagglutinin, concanavalin A, and pokeweed, whereas a normal response was seen with LPS. These studies indicate that the nude rat has absent T-cell function.
Toxicology Letters, 2006
Pesticides are designed to interfere with living species, and are inevitably characterized by var... more Pesticides are designed to interfere with living species, and are inevitably characterized by variable levels of toxicity. A number of data is at present available suggesting that the immune system may be a target of the toxic effect of pesticides.
Virchows Archiv B Cell Pathology Including Molecular Pathology, 1988
Virus Research, 1995
The helper T-cell response to the E7 protein of human papillomavirus type 16 (HPV16) was studied ... more The helper T-cell response to the E7 protein of human papillomavirus type 16 (HPV16) was studied using BALB/c (H-2d) mice. Twenty-two overlapping synthetic peptides spanning the HPV16 E7 protein were split into 6 groups. Mice were sensitized using mixtures of synthetic peptides corresponding to each of the groups. Lymph node cell suspensions were cultured with the corresponding mixture of synthetic peptides that was used for sensitization. Two mixtures induced a proliferative response. Analysis of the individual peptides from these mixtures showed that two (overlapping) peptides induced a proliferative response. This response was mediated by CD4+ cells. The common region of the two peptides was found to be a single epitope, and a minimal epitope was demonstrated (AHYNIVTFCCK). In conclusion, in contrast to others, we demonstrated a helper T-cell response in BALB/c mice. This may be due to the fact that we used synthetic peptides as immunizing agent. The helper T-cell epitopes in HPV16 E7 demonstrated previously are partly overlapping with the (minimal) epitope demonstrated here, underlining the 'public' nature of the epitope.
Veterinary Immunology and Immunopathology, 1994
In many human clinical trials and in various animal tumor models, the antitumor effect of high do... more In many human clinical trials and in various animal tumor models, the antitumor effect of high doses of systemically applied interleukin-2 (IL-2) is tested. Our studies focused on the effects of low doses of locally injected IL-2. In this paper, the effect of local injection of low doses of IL-2, i.e. a total dose of 25,000-50,000 units, into papillomas or carcinomas of the bovine vulva is described. In 19 out of 23 (83%) cows treated with IL-2 an effect on the tumor load was observed; in three of these animals, complete regression was obtained. In the majority of cases, regression was not restricted to the tumors injected with IL-2.
Toxicology Letters, 1996
The acute effects of the inhalation of air polluting agents have been examined by many research g... more The acute effects of the inhalation of air polluting agents have been examined by many research groups in both animal models and human beings. For instance, it is evident that exposure to ozone has toxic effects and can lead to lung function disturbances. For this reason it is likely that individuals suffering from COPD or asthma are groups especially at risk with'respect to the effects of ozone. The majority of studies dealing with effects of air pollutants on pulmonary allergy are restricted to IgE mediated allergy (type I allergy). Again for ozone, in animal models for type I allergy it has been demonstrated that exposure can affect the induction as well as the effector phase of this type of hyperimmune reaction (e.g. allergic asthma). Recently it has been demonstrated in animal models that non-IgE mediated 'asthma' T cells, and notably Thl cells, may play a crucial role. In a murine mode1 it was demonstrated that low molecular weight compounds can induce delayed type hypersensitivity-like reactions in the respiratory tract, and that these reactions are associated with the induction of airway hyperreactivity. Such compounds include toluene diisocyanate (TDI), to which immune responses can be readily mounted, and which can cause occupational asthma through its sensitizing capability, but to which IgE is only detected in a minority of patients suffering from TDI-associated asthma. Effects of air pollutants on Thl responses in the respiratory tract have not been studied so far. We have demonstrated that ozone can inhibit resistance to a an intratracheal challenge with Listeriu monocytogenes, indicating suppression of Thl immune responses. In addition, we have shown that ozone exposure suppresses pulmonary delayed type hypersensitivity induced by small molecular weight compounds, as well as the trachea1 hyperreactivity that is induced during the development of these immune responses, again supporting the hypothesis of suppression of Thl responses by ozone exposure. These phenomena may be due to activation of Th2 cell dependent reactions that in turn lead to a downregulation of TM mediated immunity, or to a direct effect on Thl cells or other cell types that are crucial for delayed type hypersensitivity and related airway hyperresponsiveness in this model. These data indicate that exposure to air pollutants may have differential consequences on different types of immune responses in the respiratory tract.
Toxicology Letters, 1995
This paper introduces approaches to tests for potential immunotoxicity in rodents and man and the... more This paper introduces approaches to tests for potential immunotoxicity in rodents and man and the application for evaluation of risk. Chemicals can affect the immune system. Direct effects of chemicals can result in malfunctioning of the system that can lead to decreased resistance to infections or tumors. Auto-immunity, a situation in which immune reactions to self components occur, can also be due to chemicals. Finally, chemicals can induce immune responses causing more harm to the tissue in which they take place than the chemical itself would have done. This situation is called allergy or hypersensitivity. Assessment of potential immunotoxicity can be performed in experimental animals. An array of in vivo assays of the immune system, in addition to ex vivo/in vitro assays are available to study the functional consequences of such immunotoxic effects. In particular host resistance models are valuable in this respect, since they offer endpoints that are relevant for estimation of risk to man. There is a number of examples of immunotoxic compounds. Data on direct immunotoxicity of chemicals are mainly derived from animal research, whereas detailed information in man is available only to a limited extent. The majority of such data comes from immunotherapeutic drugs, intentionally designed to influence the immune system. Environmental pollutants that are reported to have immunotoxic effects include among others dioxin and polychlorinated biphenyls oxidant gases. It is difficult at present to conclude from immunotoxic effects as they have been observed in man what their consequences are in terms of resistance to infections. Assessment of immunotoxic processes in man is difficult, as often detailed information is lacking and the immune system can only be studied to a limited extent. Although tests are available to study immune responses in man, it is often not easy to link the outcome of such assays to exposure to immunotoxicants. Few biomarkers for the immune system exist that provide specific information on the toxic activity in man and extent of exposure, or (susceptibility for) disease associated with chemical exposure.
Photochemistry and Photobiology, 1997
We analyzed natural killer (NK) cell activity in the hairless albino Skh/HR1 mouse, to study whet... more We analyzed natural killer (NK) cell activity in the hairless albino Skh/HR1 mouse, to study whether the NK cell activity plays a role during UV radiation (UVR)-induced carcinogenesis. In 4 h 51Cr-release assays, spleen lymphocytes of specific pathogen-free (spf) Skh/HR1 mice displayed 5-10% spontaneous NK cell activity. This was comparable to NK cell activity in C57B1/6, C3H and athymic NMRI nu/nu mice, which were also kept under spf conditions. In all strains investigated, the low spontaneous NK cell activity could be increased up to 20-30% by intraperitoneal administration of polyinosinic:polycytidylic acid (polyI:C), a standardized in vivo NK cell induction method. The polyI:C potentiation of NK cells in Skh/HR1 mice was similar to that in C57B1/6 and NMRI, but significantly less than in C3H mice. Chronic daily UV irradiation according to a protocol that was also used for induction of carcinogenesis (11-12 weeks, 95 mJ/cm2 of UV exposure from FS40 sunlamps) did not decrease NK cell activity on a cell for cell basis. Neither was the inducibility of NK spleen cell activity with polyI:C in Skh/HR1 mice during UV exposure reduced. Based on total organ basis, the pooled lymph node cells (axillary, mandibulary and inguinal lymph node) showed a doubling of NK cell activity (P < 0.001), mainly due to an almost 100% increase in the number of lymph node cells. In conclusion, UVR does not suppress the normal or inducible NK cell activity at the time of clinical appearance of skin tumors. This suggests that such suppression of NK cell activity is not likely to contribute to UVR-induced carcinogenesis in the Skh/HR1 strain.
Photochemistry and Photobiology, 1998
In this study we investigated the effect of the dietary ingredients fruit and vegetable, green te... more In this study we investigated the effect of the dietary ingredients fruit and vegetable, green tea phenol extract (GTP) and the specific flavonoid components quercetin and chrysin on the UV-induced suppression of the contact hypersensitivity (CHS) response to picryl chloride (PCl). The SKH-1 mice were fed with test diet from 2 or 4 weeks before and during the UV irradiation (daily, 95 mJ/cm2) and tested for the CHS ear-swelling response 10 weeks after the onset of the irradiation. For the CHS, mice were immunized with PCl by epicutaneous application on nonirradiated sites. Four days after sensitization all mice were challenged on both sides of each ear by topical application of one drop PCl. In addition, from mice fed with the fruit and vegetable mixture the number of Langerhans cells (LC) were scored in the skin and from mice fed with quercetin, quercetin levels in plasma were measured at week 11 after the start of UV irradiation. It was found that fruit and vegetable (19% in the diet), GTP (0.1% and 0.01% in the drinking water), quercetin (1% in the diet) and chrysin (1% and 0.1% in the diet), prevented statistically significantly the UV-induced suppression of CHS to PCl. In the skin of mice fed with fruit and vegetables combined with UV irradiation the number of LC were comparable to the control mice, whereas the number of LC were significantly diminished in mice treated with UV only. This protective effect on the presence of LC in the epidermis after UV irradiation, which was also observed in a previous study with quercetin, may play a role in the prevention of UV-induced immunosuppression by the flavonoids tested. In conclusion, we found protection of flavonoids against UV-induced effects on CHS, which may be a common feature of most flavonoids.
Photochemistry and Photobiology, 1997
ABSTRACT
Pediatric Allergy and Immunology, 2003
Nitric Oxide, 1999
Levels of exhaled nitric oxide (NO) were determined in well-characterized atopic and nonatopic su... more Levels of exhaled nitric oxide (NO) were determined in well-characterized atopic and nonatopic subjects on 4 days with a different level of outdoor air pollution. The two groups matched well regarding spirometric values, i.e., no difference with regard to FEV 1 , FVC, and peak flow. On the 4 test days asymptomatic atopic subjects exhaled 1.5-to 2.4-fold higher levels of NO compared with nonatopic subjects. In both groups the increase in exhaled NO in response to air pollution was similar (2.5 times maximal increase, P < 0.01). In conclusion, atopic subjects exhale higher levels of NO compared with nonatopic subjects, but respond to a similar degree to increased levels of air pollution.