The Effects of Cyclosporin A and FK-506 on the Cytokine Production of Lymphocytes in Atopic Dermatitis

ABSTRACT

BACKGROUND: It has been demonstrated that patients with atopic dermatitis(AD) show an impaired capacity of their T cells to release of interleukin-2(IL-2) in vitro and elevated serum levels of soluble IL-2 receptor(sIL-2R). Both immunosuppressive agents, cyclosporin A(CsA) and FK-506 can block early events in T lymphocyte activation and FK-506 is 10- to 100-fold more potent in the inhibition of IL-2 and other lymphokines production. OBJECTIVE: We compared the effects of CsA and FK-506 on PHA-induced lymphokine and sIL-2R production and compared the effects of CsA and FK-506 on PHA-induced IL-4 production in a high IgE group and a low IgE group in patients with AD. METHODS: A total of 32 peripheral blood samples from 17 patients with AD and 15 control groups were tested. Lymphocytes were isolated from blood samples and were cultured with PHA(positive control), PHA and CsA(10 ng/ml), PHA and FK-506 (1 ng/ml), and without stimulation (negative control). The amount of cytokines such as IL-2, IL-3, IL-4 and sIL-2R were measured using an enzyme-linked immunosorbent assay(ELISA). RESULTS: CsA and FK-506 inhibited significantly the production of IL-2, IL-3, IL-4 in PHA-stimulated lymphocytes of both the AD patients and the control groups. FK-506(1 ng/ml) inhibited cytokines production more significantly than CsA(10 ng/ml). However, CsA and FK-506 did not significantly inhibit the production of sIL-2R. There were no significant differences in the inhibitory effect of CsA and FK-506 on IL-4 production upon PHA-stimulation between AD patients with a high IgE level and with a low IgE level. CONCLUSION: Both FK-506 and CsA inhibit lymphokine production, but not the production of sIL-2R. FK-506 inhibited more significantly lymphokine production at a 10-fold lower concentration than CsA. Our data suggest that FK-506 could be more effective in the treatment of severe AD than CsA, and both these agents show their immunosuppressive activity through the suppression of lymphokine production, not via the suppression of sIL-2R production in AD.