베체트병 환자에서 말초혈액 단핵세포의 Streprococus sanguis 항원에 대한 사이토카인 생성

Abstract

Behcet´s disease is a syndrome of unknown etiology consisting of recurrent oral and genital aphthous ulcerations, ocular manifestations such as uveitis, cutaneous involvements and other inflammatory responses encompassing all systems of the body including cardiovascular, respiratory, gastrointestinal and central nervous system. The streptococcal influence on Behcet´s disease might well be emphasized, especially with regard to the S. sanguis antigen, which stimulates T cells to alter the cytokine production. Somehow, the specific cytokine species produced in this reaction still remains controversial. In this study, we have investigated the production of cytokines IFN-γ (TH1), IL-4 (TH2), in cultured supernatant after incubating inactivated S. sanguis whole cell antigens with peripheral blood mononuclear cells isolated from healthy controls, and patients in both active and inactive stages of the disease. We made use of commercially available enzyme-linked immunosorbent assay (ELISA) kit to measure the respective concentrations of these cytokines. The production fo IFN-γ was significantly increased in patients with active Behcet´s disease as compared with healthy controls or the patients with inactive diseases after 72 hours, whereas there was no significant increase of IL-4. Taking time course into consideration, IFN-γ production increased with time starting 6 hours after the incubation with the antigen and the reaction was also dose-dependent with respect to the amount of antigen. At some point IFN-γ production in patients with active disease rose in response to a very low concentration which had failed to bring out any response from healthy controls and patient with inactive disease, suggesting the hypersensitivity reaction to S. sanguis antigens by the peripheral blood mononuclear cells in patient with active disease. The duration since the onset of the symptoms and the amount of IFN-γ production showed evidences of positive correlation that was stronger than with erythrocyte sedimentation rate or C reactive protein. We conclude that IFN-γ production in patients with active Behcet´s disease differ in response to stimulation with S. sanguis antigen from that of healthy controls and inactive states, and therefore may be utilized to determine the disease activity and to evaluate the efficacy of therapeutic modalities.