Alpha-melanocyte-stimulating hormone exhibits target cell selectivity in its capacity to affect interleukin 1-inducible responses in vivo and in vitro.
The ability of i.v.-administered recombinant human interleukin 1 (IL 1 beta) to increase core body temperature, stimulate an increased production of serum amyloid P substance, and augment blood levels of circulating neutrophils in mice was inhibited in a dosage-dependent manner by administration of the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH). alpha-MSH administration was also capable of inhibiting the capacity of i.v.-administered IL 1 beta to enhance plasma levels of corticosterone and to depress the generation and/or elicitation of contact hypersensitivity responses to skin-reactive chemicals. An analog of alpha-MSH (Nle4, D-Phe7 alpha-MSH), known to be more potent than native alpha-MSH in a number of melanotropin-sensitive systems, was determined to be more active than alpha-MSH in the modification of these same in vivo responses. Neither alpha-MSH nor its analog were capable of altering the capacity of IL 1 to stimulate increased plasma levels in prostaglandin E2 (PGE2). In vitro, neither alpha-MSH nor its analog were capable of reducing the capacity of IL 1 to stimulate fibroblast production of PGE2 or to augment the proliferation of murine thymocytes exposed to phytohemagglutinin. The apparent selectivity associated with the regulatory influences of alpha-MSH on IL 1-induced responses in vivo suggests that this neuropeptide may function as an endogenous inhibitor of certain immunomodulatory and inflammatory activities of the cytokine IL 1.
D000818:Animals; D003345:Corticosterone / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000276:immunology; D015232:Dinoprostone; D005334:Fever / Q000139:chemically induced; D007375:Interleukin-1 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D009074:Melanocyte-Stimulating Hormones / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D051379:Mice; D009504:Neutrophils / Q000502:physiology; D011458:Prostaglandins E / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D000683:Serum Amyloid P-Component / Q000096:biosynthesis; D000521:alpha-MSH / Q000031:analogs & derivatives*
D007375:Interleukin-1; D011458:Prostaglandins E; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; D009074:Melanocyte-Stimulating Hormones; D015232:Dinoprostone; D003345:Corticosterone