Study summary · research use only
New insights into the functions of alpha-MSH and related peptides in the immune system
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review discusses evidence that the tridecapeptide alpha-melanocyte-stimulating hormone (alpha-MSH) and its C-terminal tripeptide KPV act on melanocortin receptor (MC-1R)-expressing monocytes, macrophages, and dendritic cells to modulate immune and inflammatory responses. The authors describe alpha-MSH down-regulating production of several proinflammatory and immunomodulating cytokines and costimulatory molecules on antigen-presenting cells while up-regulating IL-10, and cite in vivo mouse studies in which systemic and topical alpha-MSH or KPV inhibited sensitization and elicitation phases of contact hypersensitivity, induced hapten-specific tolerance mediated by CTLA4-positive and IL-10-producing T lymphocytes, and reduced allergen-specific IgE production and eosinophil influx in a murine allergic airway inflammation model via IL-10, since IL-10 knockout mice were resistant to alpha-MSH treatment.
Abstract
There is a substantial body of evidence that the tridecapeptide alpha-melanocyte-stimulating hormone (alpha-MSH) functions as a mediator of immunity and inflammation. The immunomodulating capacity of alpha-MSH is primarily because of its effects on melanocortin receptor (MC-1R)-expressing monocytes, macrophages, and dendritic cells (DCs). alpha-MSH down-regulates the production of proinflammatory and immunomodulating cytokines (IL-1, IL-6, TNF-alpha, IL-2, IFN-gamma, IL-4, IL-13) as well as the expression of costimulatory molecules (CD86, CD40, ICAM-1) on antigen-presenting DCs. In contrast, the production of the cytokine synthesis inhibitor IL-10 is up-regulated by alpha-MSH. At the molecular level, these effects of alpha-MSH are mediated via the inhibition of the activation of transcription factors such as NFkappaB. Not only alpha-MSH but also its C-terminal tripeptide (alpha-MSH 11-13, KPV) was able to bind to MC-1R and to modulate the function of APCs. In vivo, using a mouse model of contact hypersensitivity (CHS) systemic and topical application of alpha-MSH or KPV inhibited the sensitization and the elicitation phase of CHS and was able to induce hapten-specific tolerance. To investigate the underlying mechanisms of tolerance induction, we have performed in vivo transfer experiments. Treatment of naive mice with bone marrow-derived immature haptenized and alpha-MSH-pulsed DCs resulted in a significant inhibition of CHS. Furthermore, tolerance induction was found to be mediated by the generation of CTLA4(+) and IL-10-producing T lymphocytes. The potent capacity of alpha-MSH to modulate the function of antigen-presenting cells (APCs) has been further supported in another experimental approach. In vitro, by activating APCs, alpha-MSH has been shown to modulate IgE production by IL-4 and anti-CD40 stimulated B lymphocytes. Moreover, in a murine model of allergic airway inflammation, systemic treatment with alpha-MSH resulted in a significant reduction of allergen-specific IgE production, eosinophil influx, and IL-4 production. These effects were mediated via IL-10 production, because IL-10 knockout mice were resistant to alpha-MSH treatment. Therefore, therapeutic application of alpha-MSH or related peptides (KPVs) as well as alpha-MSH/KPV-pulsed DCs may be a useful approach for the treatment of inflammatory, autoimmune, and allergic diseases in the future.
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