Administration of anti-interleukin 18 antibody fails to inhibit development of dermatitis in atopic dermatitis-model mice NC/Nga

Abstract

Background: Interleukin (IL)-18 has been shown to activate basophils to produce histamine and IL-4 and to induce naive T cells to differentiate into T-helper (Th) 2 cells. However, when expressed together with IL-12, IL-18 induces Th1 cell development and inhibits IgE synthesis. Previously we reported that serum IL-18 levels were elevated in the sera from atopic dermatitis-model mice NC/Nga, prior to the onset and during the development of dermatitis. Objectives: We studied whether neutralization of IL-18 activity might affect dermatitis in NC/Nga mice, to investigate the role of IL-18 on dermatitis. Methods: NC/Nga mice were given weekly anti-IL-18 antibody starting at 5 weeks of age to 13 weeks and development of dermatitis, scratching behaviour and serum IgE concentrations were evaluated. Results: Continuous injections of anti-IL-18 antibody failed to inhibit the onset and development of dermatitis and IgE elevation. The treatment, rather, tended to lead to an exacerbation of dermatitis and scratching behaviour. In addition, the administration of anti-IL-18 antibody did not ameliorate the responsiveness of lymphocytes to IL-4, which was previously demonstrated as an immunological abnormality in the mouse. Conclusion: This study demonstrates that, at least in NC/Nga mice, IL-18, although excessively expressed before the onset of dermatitis, shows antiallergic actions.