α-MSH modulates local and circulating tumor necrosis factor-α in experimental brain inflammation

Nilum Rajora, Giovanni Boccoli, Dennis Burns, Sarita Sharma, Anna P. Catania, James M. Lipton

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor necrosis factor (TNF-α) underlies pathological processes and functional disturbances in acute and chronic neurological disease and injury. The neuroimmunomodulatory peptide α-MSH modulates actions and production of proinflammatory cytokines including TNF-α, but there is no prior evidence that it alters TNF-α induced within the brain. To test for this potential influence of the peptide, TNP-α was induced centrally by local injection of bacterial lipopolysaccharide (LPS). α-MSH given once i.c.v. with LPS challenge, twice daily intraperitoneally (i.p.) for 5 d between central LPS injections, or both i.p. and centrally, inhibited production of TNF-α within brain tissue. Inhibition of TNF-α protein formation by α-MSH was confirmed by inhibition of TNF-α mRNA. Plasma TNF-α concentration was elevated markedly after central LPS, indicative of an augmented peripheral host response induced by the CNS signal. The increase was inhibited by α-MSH treatments, in relation to inhibition of central TNF-α. Presence within normal mouse brain of mRNA for the α-MSH receptor MC-1 suggests that the inhibitory effects of α-MSH on brain and plasma TNF-α might be mediated by this receptor subtype. The inhibitory effect of α-MSH on brain TNF-α did not depend on circulating factors because the effect also occurred in brain tissue in vitro. This indicates that α-MSH can act directly on brain cells to inhibit their production of TNF-α. If central TNF-α contributes to pathology in CNS disease and injury, and promotes inflammation in the periphery, agents that act on brain α-MSH receptors should decrease the pathological TNF-α reaction and promote tissue survival.

Original languageEnglish
Pages (from-to)2181-2186
Number of pages6
JournalJournal of Neuroscience
Volume17
Issue number6
Publication statusPublished - Mar 15 1997

Keywords

  • α-MSH
  • anti-inflammatory
  • anticytokine
  • LPS
  • modulation of CNS inflammation
  • neurodegenerative disease
  • neuroimmunomodulation
  • TNF-α

ASJC Scopus subject areas

  • Neuroscience(all)

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