Specific İgE and cytokine levels in childhood hypersensitivity reactions

Immune reactions, in certain circumstances, may act as a damaging machinery in tissues and organs apart from their defending and recovering effects. Altered reactive immune response to antigens, which was mediated by the organism in destructive level, is called "allergy" or "hypersensitivity". In addition, the term "allergy" is mostly used to define anaphylactic hypersensitivity caused by IgE. Antibodies formed against allergens are not defensive ones, but IgE class specific and sensitising antibodies. These antibodies have a capability to bind mast and basophyl cells in the skin and other tissues. Allergens can normally enter an organism via respiratory and digestive systems, the skin or parenteral route. Then, regional or systemic symptoms emerge in regard with targeted shock organ. T-helper (Th) cells are divided into subgroups regarding with their lymphokine products: Th0, Thl and Th2. Thl clones produce IFN-y and IL-2, but not IL-4 and IL-5. On the other hand, Th2 cells produce IL-4, IL-5 and IL-13, but not IFN-y and IL-2 cytokines. Th0 clone has cytokine profile for the both. On the whole, lymphokines secreted by Thl cells triggers the cellular immune response by causing to the synthesis of IgM and IgG2 from B cells and inducing the macrophages. Then, they make a defence against viral, bacterial, fungal and protozoal infections. Th2 cells, which stimulate humoral immunity, have especially started a defence against certain helminth infections through IgE and IgG responses and trigger allergy. It has not been known yet by which factors the polarisation of Thl and Th2 cells is mediated in the whole framework. However, it is known that IL-12 and IL-4 are the most important cytokines, which cause to the polarisation of Thl andTh2 for the both opposite directions. The main route of this study is builded by the allergic mechanisms in which cytokines reflecting the polarisation of Thl and Th2 cells, such as IFN-y, IL-4 and IL-13, play roles. Seventy-seven children cases previously diagnosed as an allergic disease were administrated to the study by applying a detailed questionnaire and carrying out physical examination. The allergic cases presented one alone or a few of 5 clinical manifestations together in regard with their questioner and physical examination findings. No anaphylaxi case was observed, and allergic asthma was determined in 37 and urticaria in 30 cases. A control group(n=30) was formed by random selection amongst volunteer children in the same age range, living in the same area, having the same socio-economical parameters and without any allergic disease and being accepted as wholly healthy subjects by taking written concepts of their own parents. Total IgE and specific IgE levels were determined by ELISA as described by manufacturers (IgE; Int. Immuno-Diagnostics, USA, Specific IgE; Dr. Fooke, Neuss, Germany). IFN-y, IL-4, IL-13 (ELISA, CLB, Amsterdam, Netherlands) was assessed by ELISA. IgG, IgA, IgM were measured by nephelometry (Beckman Array®360 Systems, Beckman, California, USA). Assessments were carried out by using chemiluminescence kit systems for Cortisol, Chiron Diagnostics Corp. (ACS 180®, Cedex, France), for DHEAS, DPC (Immulite®2000 California, USA) as instructed by manufacturers. In statistical analysis, student's t test in independent samples, Mann- Whitney U test, correlation (Spearman) and multiple regression analyses were applied by using SPSS 6.0 for Windows 95. When considered the whole allergic cases, total IgE levels were found to be higher in allergic cases than the controls. No statistically significant difference was observed, when compared levels of IgG, IgA and IgM in allergic cases with the healthy individuals. As to relationships of cytokines IFN-y, IL-4 and IL-13 with total IgE mentioned above, it was found that IFN-y and IL-4 were not correlated with total IgE, and IL-13 showed negative but not statistically significant correlation. These results indicate that it is not possible to evaluate Thl and Th2 polarisation by just investigating the relationship between cytokines and total IgE. In this study, while IFN-y diminished in allergic cases when compared to the control group, IL-4 elevated approximately 10-fold and IL-13 approximately 7-fold. These results approve the in vivo effects of both cytokines on IgE synthesis. It is in vivo shown in this study that there is a statistically significant negative correlation between IFN-y and IL-4. This is a finding explaining the polarisation of Thl and Th2 lymphocyte subgroups. Not observing the same relationship between IFN-y and IL-13 make strong the possibility of IL-13 to be abundantly produced by some other cells. In this study, the relationship amongst levels of hormones, DHEA and Cortisol, and cytokines such as IL-4, IL-13 and IFN-y indicatory for Thl/Th2 polarisation. When compared all the allergic cases for DHEA and Cortisol levels, it was observed that Cortisol levels increased and DHEA levels did not alter in allergic cases. The elevation of Cortisol levels may lead to triggering Th2 cells by suppressing Thl cells, and this may create the main reason of allergy. On the other hand, there was a statistically significant correlation between total IgE and Cortisol levels. However, it was necessary to find negative correlation between Cortisol and IFN-y levels, and positive correlation between Cortisol and IL-4 levels to complete the loop-mechanism. When considered asthma and urticaria cases separately, it was observed that Cortisol levels elevated, but DHEA-S04 levels did not alter. In allergic asthma cases, observing the statistically significant correlation between elevations of DHEA and IL-13 levels approves the hypothesis for mediatory role of DHEA in Th2 cell polarisation. However, as happened in urticaria cases, absence of a correlation between other cytokines and IgE and not altering of IL-4 and IFN-y by DHEA levels do not give the chance to complete the hypothetical picture mentioned above. In the study, a significant positive correlation was observed between Cortisol and total IgE levels in children with urticaria. The same relationship was not found, when statistically considered the whole allergic and asthma cases. Consequently, this study was carried out to enlighten Thl and Th2 polarisation in vivo in allergy. On the basis of the study, suppression of IL-4 and IL-13 production or blockage of them by antibodies, or diminishing of Th2 population and then their cytokine production via maintenance of Thl dominancy by IFN-y administration may take an important place in Type I allergy treatment in future.