There is accumulating evidence for a strong interaction between components
of the nervous system and the immune system. Accordingly, specific receptor
s for neuropeptides were found to be expressed on immunocompetent cells and
several neuropeptides were recognized as potent regulators of immune and i
nflammatory reactions. Among various neuropeptides such as substance P, cal
citonin gene-related peptide and others alpha-melanocyte-stimulating hormon
e (alpha-MSH) was found to be produced in the skin, Moreover, melanocortin
receptor 1 which is specific for alpha-MSH and ACTH is expressed in the ski
n on keratinocytes, dendritic cells, macrophages and endothelial cells. In
monocytes, macrophages and dendritic cells alpha-MSH inhibits the productio
n and activity of immunoregulatory and proinflammatory cytokines such as IL
-2, IFN gamma and IL-l, it downregulates the expression of costimulatory mo
lecules such as CD86 and CD40 and induces the production of suppressor fact
ors such as the cytokine synthesis inhibitory factor IL-10. On endothelial
cells alpha-MSH is capable of downregulating the LPS-induced expression of
adhesion molecules such as vascular cellular adhesion molecules and E-selec
tin. Moreover, the LPS-induced activation of transcription factors such as
NF kappa B is downregulated by alpha-MSH. In a mouse model intravenous or t
opical application of alpha-MSH was found to inhibit the induction as well
as the effector phase of a contact hypersensitivity reaction and to induce
hapten-specific tolerance. Moreover, there is evidence that the N-terminal
tripeptide of alpha-MSH is sufficient for its in vitro and in vivo immunomo
dulatory effects. These findings indicate that the production of immunosupp
ressing neuropeptides such as alpha-MSH by epidermal cells may play an esse
ntial role during the pathogenesis of immune and inflammatory reactions in
the skin. Copyright (C) 2000 S. Karger AG, Basel.