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Papers by C Goebel
Rheumatology, 1994
Following weekly i.m. injections of gold(I) disodium thiomalate (GST), mice of strains A.SW and C... more Following weekly i.m. injections of gold(I) disodium thiomalate (GST), mice of strains A.SW and C57BL/6 develop adverse immune reactions, whereas DBA/2 mice do not. We have studied the pharmaco-toxicokinetics of gold in these strains under chronic GST treatment. Our results indicate that the susceptible strains A.SW and C57BL/6 accumulate significantly higher gold concentrations in the liver and spleen compared to the resistant strain DBA/2. In the kidney of DBA/2 mice, gold concentrations persisted at a plateau level, whereas in A.SW and, particularly, C57BL/6 mice early peaks of gold concentrations were followed by a transient decrease, suggestive of tubular toxicity. Whereas splenic T and B cells failed to contain measurable gold concentrations in all three strains, splenic and peritoneal macrophages contained relatively high levels, more so in the susceptible strain C57BL/6 than in the resistant DBA/2 strain. This finding is consistent with the concept that macrophages play an important role in both the adverse and the beneficial effects of gold drugs.
Life Sciences, 1999
The impact of exposure to lead on gut cytokine gene expression and oral tolerance was analyzed. O... more The impact of exposure to lead on gut cytokine gene expression and oral tolerance was analyzed. Oral tolerization with ovalbumin (OVA) increased levels of IL-10 and TGF-R in gut tissue while IFN-)I mRNA levels remained unchanged in both autoimmune diabetes prone NOD and normal C57BLi6 mice. This shift towards Th2iTh3 type cytokine gene expression was completely abolished by concomitant treatment with PbCl? (6 x 0.5 mg/kg) in NOD mice while the cytokine balance in C57BLi6 mice was unaffected. Suppression of ThYTh3 type cytokine expression was associated with a dampened oral tolerance response to OVA as determined by T cell proliferation assays. We conclude that in autoimmunity prone NOD mice environmental toxicants may disturb immune homeostasis by targeting the gut immune system.
Diabetes/Metabolism Research and Reviews, 2002
Background The goal of the present study was to determine whether cytokines in the peripheral blo... more Background The goal of the present study was to determine whether cytokines in the peripheral blood of naive NOD mice correlate with the disease process and thereby would provide a marker for monitoring disease activity. Methods Female NOD mice (5, 10 and 14-16 weeks of age) were investigated in a cross-sectional study. In the group of 14-16-week-old mice, non-diabetic and diabetic mice were analysed as different subgroups. The Th1 cytokine (IFN-c) and the Th2 cytokine (IL-10) were quantified in serum by sandwich enzyme-linked immunosorbent assay (ELISA). Pancreatic mRNA for IFN-c and IL-10 was determined by reverse transcriptasepolymerase chain reaction (RT-PCR) from the same animals. Results Serum levels of IFN-c were initially low but increased with age in NOD mice, reaching the highest levels at diabetes onset (p<0.002 compared to 10 weeks). A similar rise was noted in IFN-c gene expression in pancreatic lesions. In contrast, an early peak of serum IL-10 levels was observed in nondiabetic NOD mice (10 weeks) at a stage where non-destructive insulitis occurs. With increasing age a continuous loss of IL-10 until progression towards diabetes was observed. The pancreatic IL-10 mRNA expression correlated with serum IL-10 changes. As a consequence, the ratio of IFN-c/ IL-10, reflecting the Th1/Th2 balance in the serum, was significantly increased in diabetic compared to non-diabetic NOD mice (p<0.005). Conclusion These results demonstrate, for the first time, that an increased Th2 pattern in the non-diabetic stage preceding a Th1 shift is associated with the development of diabetes in naive NOD mice. Serum cytokines correlate with disease progression and pancreatic cytokine expression during prediabetes. Soluble cytokines measured in the periphery are therefore promising surrogate markers of diabetes development.
Rheumatology, 1994
Following weekly i.m. injections of gold(I) disodium thiomalate (GST), mice of strains A.SW and C... more Following weekly i.m. injections of gold(I) disodium thiomalate (GST), mice of strains A.SW and C57BL/6 develop adverse immune reactions, whereas DBA/2 mice do not. We have studied the pharmaco-toxicokinetics of gold in these strains under chronic GST treatment. Our results indicate that the susceptible strains A.SW and C57BL/6 accumulate significantly higher gold concentrations in the liver and spleen compared to the resistant strain DBA/2. In the kidney of DBA/2 mice, gold concentrations persisted at a plateau level, whereas in A.SW and, particularly, C57BL/6 mice early peaks of gold concentrations were followed by a transient decrease, suggestive of tubular toxicity. Whereas splenic T and B cells failed to contain measurable gold concentrations in all three strains, splenic and peritoneal macrophages contained relatively high levels, more so in the susceptible strain C57BL/6 than in the resistant DBA/2 strain. This finding is consistent with the concept that macrophages play an important role in both the adverse and the beneficial effects of gold drugs.
Life Sciences, 1999
The impact of exposure to lead on gut cytokine gene expression and oral tolerance was analyzed. O... more The impact of exposure to lead on gut cytokine gene expression and oral tolerance was analyzed. Oral tolerization with ovalbumin (OVA) increased levels of IL-10 and TGF-R in gut tissue while IFN-)I mRNA levels remained unchanged in both autoimmune diabetes prone NOD and normal C57BLi6 mice. This shift towards Th2iTh3 type cytokine gene expression was completely abolished by concomitant treatment with PbCl? (6 x 0.5 mg/kg) in NOD mice while the cytokine balance in C57BLi6 mice was unaffected. Suppression of ThYTh3 type cytokine expression was associated with a dampened oral tolerance response to OVA as determined by T cell proliferation assays. We conclude that in autoimmunity prone NOD mice environmental toxicants may disturb immune homeostasis by targeting the gut immune system.
Diabetes/Metabolism Research and Reviews, 2002
Background The goal of the present study was to determine whether cytokines in the peripheral blo... more Background The goal of the present study was to determine whether cytokines in the peripheral blood of naive NOD mice correlate with the disease process and thereby would provide a marker for monitoring disease activity. Methods Female NOD mice (5, 10 and 14-16 weeks of age) were investigated in a cross-sectional study. In the group of 14-16-week-old mice, non-diabetic and diabetic mice were analysed as different subgroups. The Th1 cytokine (IFN-c) and the Th2 cytokine (IL-10) were quantified in serum by sandwich enzyme-linked immunosorbent assay (ELISA). Pancreatic mRNA for IFN-c and IL-10 was determined by reverse transcriptasepolymerase chain reaction (RT-PCR) from the same animals. Results Serum levels of IFN-c were initially low but increased with age in NOD mice, reaching the highest levels at diabetes onset (p<0.002 compared to 10 weeks). A similar rise was noted in IFN-c gene expression in pancreatic lesions. In contrast, an early peak of serum IL-10 levels was observed in nondiabetic NOD mice (10 weeks) at a stage where non-destructive insulitis occurs. With increasing age a continuous loss of IL-10 until progression towards diabetes was observed. The pancreatic IL-10 mRNA expression correlated with serum IL-10 changes. As a consequence, the ratio of IFN-c/ IL-10, reflecting the Th1/Th2 balance in the serum, was significantly increased in diabetic compared to non-diabetic NOD mice (p<0.005). Conclusion These results demonstrate, for the first time, that an increased Th2 pattern in the non-diabetic stage preceding a Th1 shift is associated with the development of diabetes in naive NOD mice. Serum cytokines correlate with disease progression and pancreatic cytokine expression during prediabetes. Soluble cytokines measured in the periphery are therefore promising surrogate markers of diabetes development.