IL-33/13 Axis and IL-4/31 Axis Play Distinct Roles in Inflammatory Process and Itch in Psoriasis and Atopic Dermatitis (original) (raw)
Related papers
Allergy, 2014
Background: The most intriguing function attributed to interleukin-31 (IL-31) is its ability to induce pruritus in pathologic conditions, such as atopic dermatitis (AD). As of today, this feature of IL-31 was tested in vivo only in animal models. Methods: Ten patients with AD and 10 healthy controls were challenged with IL-31 and NaCl (negative control) by skin prick testing. Twenty additional healthy controls were subjected to skin prick testing with histamine. Itch and local inflammatory responses of the skin were assessed for up to 72 h. Results: All of the histamine-challenged subjects developed immediate pruritus (i.e. within the first 5 min). In contrast, only one IL-31-and two of the NaClchallenged subjects reported immediate itch at the provocation site (short lasting, for 2-6 min). Nine subjects (five patients with AD) reported late itch responses to IL-31 challenges with a mean delay of 143 min. No subject reported late itch responses to histamine or NaCl testing. There was no significant difference in IL-31-induced itch start time, duration and intensity between patients with AD and healthy volunteers. Conclusion: IL-31 does not induce immediate itch responses in humans. The late onset of IL-31-induced itch supports the notion that IL-31 exerts its pruritic effect indirectly via keratinocytes and secondary mediators, rather than through its receptors on cutaneous nerves.
Journal of Allergy and Clinical Immunology, 2006
Background: IL-31 is produced by activated T lymphocytes, preferentially by T H 2 cells. Transgenic mice overexpressing IL-31 have a phenotype resembling allergic dermatitis in human subjects. Objective: We sought to evaluate the potential importance of IL-31 in the pathogenesis of human T cell-mediated skin diseases. Methods: We analyzed total RNA taken from 149 skin biopsy specimens from patients with atopic dermatitis (AD), allergic contact dermatitis (ACD), or psoriasis in comparison with specimens taken from patients with healthy skin (n 5 13) by using quantitative real-time PCR for the expression of T H 1/T H 2 cytokines. Results: We found statistically increased mRNA levels of IL-31 in biopsy specimens taken from patients with AD, irrespective of the severity of the disease and serum IgE levels. Moreover, IL-31 mRNA levels were strongly increased in many biopsy specimens taken from patients with ACD. However, no increased transcription of IL-31 could be detected in biopsy specimens taken from psoriatic plaques. A comparison of mRNA levels of IL-31 with T H 1 or T H 2 cytokines demonstrates a correlation of the expression of IL-31 with IL-4 and IL-13 but not with IFN-g. No significant increase of IL-31 receptor mRNA could be detected in any disease, whereas the second receptor subunit of IL-31, the oncostatin M receptor, seems to be enhanced transcribed in patients with psoriasis.
IL-31 Expression by Inflammatory Cells is Preferentially Elevated in Atopic Dermatitis
Acta Dermato Venereologica, 2012
Interleukin-31 (IL-31) is a recently discovered cytokine expressed in many human tissues, and predominantly by activated CD4 + T cells. IL-31 signals through a heterodimeric receptor consisting of IL-31 receptor alpha (IL-31RA) and oncostatin M receptor beta (OSMR). Earlier studies have shown involvement of IL-31 and its receptor components IL-31RA and OSMR in atopic dermatitis, pruritus and Th2-weighted inflammation at the mRNA level. The aim of this study was to investigate IL-31 protein expression in skin of such conditions. Immunohistochemical staining for IL-31, IL-31RA and OSMR was performed in formalin-fixed paraffin-embedded biopsy specimens. IL-31 expression was increased in the inflammatory infiltrates from skin biopsies taken from subjects with atopic dermatitis, compared with controls (p ≤ 0.05).
2022
Background: Itching is one of the major and mandatory signs of atopic dermatitis (AD) in children. Interleukin 31 (IL-31) is strongly involved in the genesis of pruritus. In our study, 68 patients aged 0-18 years with proven AD were followed clinically. The role of IL-31 in pruritus as clinical manifestation of AD is known but its etiopathogenetic mechanism is not well known. Methods: Serum was collected from 31 patients with moderate and severe forms of AD to determine IL-31 and its correlation with activity and severity of the disease. We also studied 30 healthy patients to compare the results of determinations. The IL-31 value was determined using the sandwich enzyme-linked-immunosorbent serologic assay (two antibodies assay). The IL-31 values were expressed as picograms per milliliter (pg/mL) and compared with activity and severity of the disease. Results: The IL-31 value was much higher in patients with AD compared to the control group. The mean value of findings was 1600 pg/mL compared to the control group with an average of 220 pg/mL. The IL-31 values were positively correlated with the severity and activity of the disease. Conclusions: The results of our pediatric study established the involvement of IL-31 in the pathophysiology of AD. IL-31 could be a marker of AD track.
Advances in Dermatology and Allergology
Introduction: Interleukin-31 (IL-31) impact on the development and clinical presentation of psoriasis as well as pruritus has not been widely investigated so far. Aim: To analyse IL-31-1066G/A and-2057G/A promoter gene polymorphisms as well as serum IL-31 level and their correlation with severity of psoriasis and pruritus in the population of northern Poland. Material and methods: The study included 300 psoriasis patients and 186 healthy volunteers. The polymorphisms were analysed using amplified refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Serum levels of IL-31 were measured using the enzyme-linked immunosorbent assay (ELISA) test. Results: The-1066 AA genotype of the IL-31 gene was statistically more frequent in patients and it increased the risk of psoriasis (OR = 1.80; p = 0.04). The GG genotype as well as G allele of the IL-31-2057 gene polymorphism were rarely observed in psoriasis and were associated with a decreased risk of the disease (OR = 0.6, p = 0.007 and OR = 0.7, p = 0.01, respectively). Serum levels of IL-31 were significantly elevated in psoriasis patients (p < 0.000001), however, they did not correlate with the studied polymorphic variants of the IL-31 gene, severity of psoriasis, disease onset, presence of psoriatic arthritis and pruritus intensity. Conclusions: Distinct IL-31 promoter gene polymorphisms may be involved in psoriasis development. It seems that serum concentration of IL-31 may not be a reliable marker of psoriatic pruritus.
Acta dermato-venereologica, 2014
A slight epidermal damage can induce the Köbner reaction in psoriasis, and the "alarmin", interleukin-33 (IL-33), may be involved in this process. Therefore, the uninvolved psoriatic skin was tape-stripped, and skin biopsies were collected at 0d, 2h and 3d or at 0d, 1d and 7d for immunohistochemistry. Eight patients out of 18 with the positive Köbner reaction showed a decrease in epidermal thickness and revealed transient reduction in epidermal nuclear immunostaining of IL-33 in 2h-1d-3d biopsies compared to the 10 Köbner-negative patients. In keratinocyte cultures, the full-length 32-kDa IL-33 was detected after damaging the cells with freeze-thawing. Interestingly, a very low concentration of rh-IL-33 (0.001-0.01 ng/ml) significantly stimulated 3H-thymidine uptake by human LAD2 mast cells, but not by psoriatic peripheral blood mononuclear cells. The results show that epidermal IL-33 associates with positive Köbner response, and only a small amount of the IL-33 apparently...
The role of interleukin-1ß and interleukin-33 in atopic dermatitis
Our Dermatol Online , 2013
Introduction: Interleukin-1 super family is a group of cytokines that play a role in the regulation of immune and inflammatory responses. Interleukin-33 is a member of this family and is known to induce expression of the T helper2 cytokines that are important players in atopic dermatitis. Aim: To evaluate the expression of interleukins-1ß and 33 as T helper2 cytokines inducers in patients with atopic dermatitis. Materials and Methods: This study included 20 atopic patients and 20 apparently healthy individuals serving as controls. Skin biopsies from all participants will be examined for detection of interleukins-1ß and 33 by ELISA technique. Results: Both interleukins were statistically higher (P<0.001) in patients than in controls. A statistically significant (P=0.011) highest levels of interleukin-33 was detected in severe cases of atopics when compared to mild and moderate cases. A significant correlation (r=0.632, P=0.003) between both interleukins was detected in atopics. Conclusions: This is the first study to evaluate both interleukin-1ß and33 together in atopic patients. Both interleukins could play a role in the recruitment of lymphocytes during the inflammatory reaction in atopic dermatitis and could be targeted in the treatment of resistant cases.
Journal of Dermatological Science, 2003
Background: Interleukin (IL)-13 is a pleiotropic cytokine, which shares many biological functions with IL-4. The receptor subunits of IL-13 consist of IL-4Ra, IL-13Ra1 and IL-13Ra2. The regulatory mechanisms of the IL-13Ra expression in the keratinocytes of certain skin disease have not been known. Objective: To clear the roles of IL-13 and the regulatory mechanisms of its receptor in atopic dermatitis (AD) and psoriasis. Method: The expression of IL-13Ra1 in the skin of AD and psoriasis was investigated by immunohistochemistry. The regulation of IL-13Ra mRNA in the skin and human primary keratinocyte (HPK) was investigated by quantitative PCR. The secretion of IL-6 and RANTES from HPK was measured by ELISA. Results: The expression of IL-13Ra1 was more prominent on the suprabasal keratinocytes in the skin of AD and striking increase of staining was observed on all layers of keratinocyte in the skin of psoriasis. The mRNA of IL-13Ra1, but not of IL-13Ra2 was overexpressed in both skin of AD and psoriasis. In vitro experiment using HPK demonstrated that IFNg, IL-13 but not IL-4 could up-regulate the mRNA expression of IL-13Ra1. In contrast, IL-13Ra2 mRNA expression was up-regulated by IFN-g plus IL-4. Furthermore, the stimulation of HPK with IFN-g plus IL-13 and/or IL-4 resulted in significant enhancement of IL-6 and RANTES secretion. Conclusion: These findings indicate that IL-4 and IL-13 have different regulatory effects on the expression of IL-13Ra1 and a2, and the overexpression of IL-13Ra1 may play some roles in the pathogenesis of chronic stage of AD or psoriasis.
Experimental Dermatology, 2012
IL-33 is a novel pro-inflammatory cytokine and ligand for the orphan receptor ST2. Although originally defined as an inducer of Th2-mediated responses, IL-33 was recently found to be involved in arthritis, a Th1/Th17-mediated disease. Here, we assessed the ability of IL-33 to promote inflammation via mast cells (MCs) and keratinocytes (KCs) activation in psoriasis. IL-33 resulted elevated in the skin but not in the serum of psoriasis patients. IL-33 was secreted by psoriasis KCs and HaCaT cells after TNF-a stimulation. In HMC-1, TNF-a, but not IL-17, could induce a robust increase in IL-33 expression. In HaCaT cells, TNF-a was able to induce IL-6, MCP-1 and VEGF, and the addition of IL-33 reinforced these increases. TNF-a + IL-33 combination showed similar results in primary KCs and ex vivo skin organ culture. In conclusion, our study suggests that IL-33 may be involved in psoriasis biology via MCs and KCs.