A. Macaluso et al., ANTIINFLAMMATORY INFLUENCES OF ALPHA-MSH MOLECULES - CENTRAL NEUROGENIC AND PERIPHERAL ACTIONS, The Journal of neuroscience, 14(4), 1994, pp. 2377-2382
alpha-Melanocyte-stimulating hormone (alpha-MSH(1-13)) and its COOH-te
rminal tripeptide alpha-MSH(11-13) (Lys Pro Val) inhibit inflammation
when administered systemically. Recent evidence indicates that alpha-M
SH(1-13) can likewise inhibit inflammation in the skin solely via an a
ction within the brain. Because of the potential importance of this di
scovery to understanding the control of inflammation and because alpha
-MSH molecules might be useful for treatment of inflammation, experime
nts were performed to learn more about the mechanisms of action of the
se peptides. In tests on inflammation induced in the mouse ear by intr
adermal injections of recombinant human interleukin-1 beta, alpha-MSH(
1-13) administered intracerebroventricularly effectively reduced infla
mmation. This effect of centrally administered alpha-MSH(1-13) was inh
ibited by systemic injection of the nonspecific beta-adrenergic recept
or blocker propranolol and by administration of a specific beta(2)-adr
energic receptor antagonist; the effect was not altered by blockade of
cholinergic, alpha-adrenergic, or beta(1)-adrenergic receptors. In mi
ce with inflammation induced in a hind paw and with the spinal cord tr
ansected, the antiinflammatory effect of centrally administered alpha-
MSH(1-13) was prevented, indicating that intact descending neuronal pa
thways are required for the antiinflammatory influence of the central
peptide. Systemic injection of alpha-MSH(1-13) in animals with spinal
cord transection had a smaller and later antiinflammatory effect, whic
h suggests that the molecule also has an action, albeit lesser, in the
periphery. However, alpha-MSH(11-13) injected intraperitoneally had m
arked antiinflammatory activity in animals with spinal cord transectio
n. The combined evidence indicates that alpha-MSH(1-13) has both centr
al and peripheral sites of action in modulation of inflammation; the c
entral effects of alpha-MSH(1-13) are mediated by pathways that involv
e peripheral beta(2)-adrenergic receptors; the antiinflammatory/antipy
retic message sequence of alpha-MSH(1-13), alpha-MSH(11-13), has poten
t antiinflammatory activity when given systemically, activity that doe
s not require intact spinal cord pathways.