Influence of alpha-melanocyte stimulating hormone on induction of contact hypersensitivity and tolerance.
Tumor necrosis factor-alpha (TNF-alpha) 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 alpha-melanocyte stimulating hormone (alpha-MSH) is generated within ultraviolet B-exposed skin, experiments were conducted to determine whether the cutaneous immune deficit caused by alpha-MSH is mediated by a TNF-alpha-dependent pathway, and/or whether alpha-MSH is responsible for UVB-induced tolerance. When dinitrofluorobenzene was painted on alpha-MSH-treated skin of ultraviolet B-susceptible and ultraviolet B-resistant strains of mice, only weak contact hypersensitivity was induced. However, neutralizing anti-TNF-alpha antibodies failed to restore contact hypersensitivity responsiveness to mice treated with alpha-MSH. Moreover, mice that first encountered hapten via alpha-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 alpha-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.
Shimizu
T
T
Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
Streilein
J W
JW
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D003877:Dermatitis, Contact / Q000209:etiology* / Q000503:physiopathology*; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D006241:Haptens / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011836:Radiation Tolerance / Q000502:physiology*; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D014466:Ultraviolet Rays; D000521:alpha-MSH / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
D000906:Antibodies; D006241:Haptens; D014409:Tumor Necrosis Factor-alpha; D000521:alpha-MSH; D004139:Dinitrofluorobenzene