Alpha melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin 1.
Abstract
Abstract The ability of interleukin 1 (IL 1) to augment the proliferation of murine thymocytes in vitro was inhibited in a dose-dependent manner by the neuropeptide alpha-melanocyte-stimulating hormone (alpha MSH). The minimal effective concentration of alpha MSH was 10(-11) M. Maximal effect occurred between 10(-8) and 10(-7) M, with diminishing effectiveness at higher concentrations. IL 1-induced production of prostaglandin E (PGE) by fibroblasts was also inhibited by alpha MSH with a biphasic dose response. The minimal effective concentration was 10(-11) M, and maximum effect was achieved at 10(-10) M. alpha MSH appeared to affect the interaction of IL 1 with its target cells in a specific manner, because it did not inhibit basal mitogen-induced thymocyte proliferation or IL 2-induced proliferation of a cytotoxic T lymphocyte line. Furthermore, production of IL 1 by endotoxin-stimulated monocytes was not affected by alpha MSH. An analog of alpha MSH (Nle4, d-Phe7 alpha MSH), which is highly potent in other melanotropin-sensitive systems, did not affect the action of IL 1 on thymocytes, suggesting that the immunomodulatory effects of alpha MSH may not be mediated by the classic melanocyte alpha MSH receptor. The influence of alpha MSH on thymocytes and fibroblasts suggests that alpha MSH is an endogenous antagonist of IL 1, perhaps important for limiting inflammatory damage to host tissues.
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Cited By (21)
- Targeting melanocortin receptors as a novel strategy to control inflammationPharmacological Reviews · 2004
- Anti-inflammatory actions of the neuroimmunomodulator α-MSHImmunology Today · 1997
- α-Melanocyte-Stimulating Hormone and Related Tripeptides: Biochemistry, Antiinflammatory and Protective Effects in Vitro and in Vivo, and Future Perspectives for the Treatment of Immune-Mediated Inflammatory DiseasesEndocrine Reviews
- In vitro induction of CD25+ CD4+ regulatory T cells by the neuropeptide alpha‐melanocyte stimulating hormone (α‐MSH)Immunology and Cell Biology · 2001
- α-Melanocyte-Stimulating Hormone Inhibits Allergic Airway InflammationThe Journal of Immunology · 2003
- Sick building syndrome (SBS) and exposure to water-damaged buildings: Time series study, clinical trial and mechanismsNeurotoxicology and Teratology · 2006
- Identification of alpha-melanocyte stimulating hormone as a potential immunosuppressive factor in aqueous humor
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