Correlations between serum levels of IL-17, IL- 4, IL-31, IFN-gamma and etiological factors in patients with chronic spontaneous urticaria

Introduction Chronic urticaria is a frequent disease that substantially affects quality of life of affected patients at a level comparable to that of patients suffering from heart diseases, on the waiting list for triple coronary artery bypass surgery (O’Donnell et al 1997). It is estimated that about 3% of the population of Western Europe suffer from chronic urticaria and the same disorder is reported in 1% of the total population of the United States. In a study conducted in Romania in 1995 (Kaplan et al 2009), a 1.9% prevalence of urticaria was assessed. Urticaria is defined by the appearance of erythematous, edematous pruritic papular lesions that quickly appear and disappear (last up to 24 hours). It can occur with or without angioedema, when the process affects the deeper layers of the dermis or the subcutaneous tissue. When the evolution of the rash is longer than 6 weeks, it is defined as chronic urticaria. Chronic urticaria can be caused by various agents (infections, parasitic infestations, hormonal disorders, autoimmune diseases, adverse drug reactions, atopy, food allergies), but research shows that the formation of IgG anti-FcεRIα and more rarely, anti-IgE, detected by an autologous serum skin test, or by the test assessing histamine release from mast cells, is the cause of 30-50% of cases of chronic urticaria in adults and up to 80% in children (Guttman et al 2007, Jang et al 2007, Mari 2004). Genetics also plays an important role in the occurrence of chronic urticaria, so there is a significant association between HLA class II histocompatibility antigens and chronic urticaria. The prevalence of DRB1*04 (DR4) and of DQB1*0302 (DQ8) allele is significantly increased in patients with chronic urticaria. HLA-DR4, in particular, is associated with a positive autologous serum skin test (Dillon et al 2004). Interleukin 31 (IL-31) is a cytokine produced by activated T cells. Its structure makes it a member of the IL-6 family of cytokines. Memory T cells, able to produce IL-31, are present in the skin, where they can contribute to the occurrence of inflammation. IL-31 is considered to be an IL that can lead to skin inflammation. In experimental mouse studies, IL-31 overexpression induces pruritus and dermatitis, similar to those seen in humans (Dillon et al 2004). IL-31 was associated with atopic dermatitis (Sonkoly et al 2006, Nobbe et al 2012), contact dermatitis, and allergic respiratory diseases. IL-17 is another pro-inflammatory cytokine secreted by Th17 cells, a subset of T helper cells, discovered in 2007. IL 17 is a cytokine which acts as a mediator in delayed-type reactions by increasing chemokine production in various tissues in order to recruit monocytes and neutrophils to the site of inflammation, similar to interferon γ. Due to the involvement of IL-17 in autoimmune diseases, there have been multiple studies on ways to inhibit its secretion, obtaining promising results in rheumatoid arthritis, inflammatory bowel disease, and especially in psoriasis . Abstract. Chronic urticaria is a skin disease with an important immunologic profile, which necessitates substantial investigations especially regarding the cytokine’s profile. It is a well-known fact that 35-40% of patients have autoimmune chronic urticarial. Objective: to identify the presence of some etiological factors in patients with chronic urticaria, and to correlate them with interleukin 17 (IL 17), interleukin 4, interleukin 31 and interferon gamma (INF-G). Material and method: We included 59 patients diagnosed with chronic urticaria, and 15 healthy subjects. Patients with urticaria followed an etiologic screening and filled a questionnaire of disease activity (urticaria activity score – UAS, recommended by EAACI/GA2LEN/WAO Guidelines). Also, blood was collected from patients and controls, in order to determine the seric level of interleukin 17 (IL 17), interleukin 4, interleukin 31 and interferon gamma (IFN-γ). Results: The seric levels of IFN-G and IL 17 were significantly higher in patients which tested positive to autolog serum (p=0.001; p=0.01 respectively). IFN-γ value was higher in those with concomitant infectious disease (p=0.001). In those with atopic syndrome, levels of IL 31 were elevated (p=0.001). UAS was correlated with IL 17 and IL 3. Conclusion: Our study showed that the cytokines profile in chronic urticaria is a mixt one, and is related to the presence of some etiologic factors