Influence of alpha-melanocyte stimulating hormone on induction of contact hypersensitivity and tolerance

Abstract

Tumor necrosis factor-alpha (TNF-α) has been demonstrated to be the primary molecular mediator of impaired contact hypersensitivity induction after ultraviolet B radiation, but the mediator of ultraviolet B-induced tolerance remains obscure. Since α-melanocyte stimulating hormone (α-MSH) is generated within ultraviolet B-exposed skin, experiments were conducted to determine whether the cutaneous immune deficit caused by α-MSH is mediated by a TNF-α-dependent pathway, and/or whether α-MSH is responsible for UVB-induced tolerance. When dinitrofluorobenzene was painted on α-MSH-treated skin of ultraviolet B-susceptible and ultraviolet B-resistant strains of mice, only weak contact hypersensitivity was induced. However, neutralizing anti-TNF-α antibodies failed to restore contact hypersensitivity responsiveness to mice treated with α-MSH. Moreover, mice that first encountered hapten via α-MSH-treated skin failed to acquire tolerance; instead, these mice retained the ability to develop and display intense contact hypersensitivity when hapten was painted subsequently on normal (untreated) skin. We conclude that α-MSH can interfere with contact hypersensitivity induction, but cannot be considered a mediator of ultraviolet B-induced tolerance because skin treated with this neuropeptide does not support tolerance induction when hapten is applied epicutaneously.