Background: IL-10 is known as a negative regulator for inflammatory diseases, including contact dermatitis. However, only a few drug candidates are reported to induce endogenous IL-10.
Objective: We sought to elucidate a new mechanism underlying the immunosuppressive properties of astilbin through negative cytokine regulation in comparison with the effective pattern with cyclosporin A.
Methods: Contact hypersensitivity was induced in mice with picryl chloride. Lymph node cells were isolated for adoptive transfer and cytokine assays.
Results: Astilbin significantly inhibited contact hypersensitivity when given in the elicitation phase but not in the sensitization phase, whereas cyclosporin A inhibited both phases. Lymph node cells from donor mice administered astilbin failed to adoptively transfer the hypersensitivity. Astilbin in vivo remarkably induced IL-10 expression in lymph node cells at an earlier time and decreased TNF-alpha and IFN-gamma expression at a later time. Furthermore, the in vivo neutralization of IL-10 significantly impaired the effect of astilbin on contact hypersensitivity. In the isolated lymphocytes sensitized with picryl chloride in vivo and challenged with trinitrobenzene-sulfonic acid in vitro, astilbin did not affect the cell proliferation but modulated the above cytokine profiles as its in vivo effect in a concentration-dependent manner and furthermore significantly enhanced the expressions of suppressor of cytokine signaling 1 and 3. On the other hand, cyclosporin A strongly inhibited proinflammatory cytokine production but influenced neither IL-10 nor downstream suppressor of cytokine signaling 1 and 3 expression.
Conclusion: Astilbin alleviates contact hypersensitivity through a unique mechanism involving a negative cytokine regulation through stimulating IL-10, which is distinct from the immunosuppressant cyclosporin A.