Neuropeptide regulation of proinflammatory cytokine responses

Camille Dickerson, Bradley Undem, Brandon Bullock, Richard A. Winchurch

Research output: Contribution to journalArticle

Abstract

Severe traumatic injuries and infections are frequently accompanied by life-threatening shock and are associated with increases in the proinflammatory cytokines, particularly tumor necrosis factor α (TNF-α). The body's first perception of injury is the nociceptive or pain response. This response is induced at the site of injury and is transmitted systemically by sensory neuropeptides, the tachykinins, released from sensory afferent c-fiber neurons. We studied the role of tachykinins in regulating the production of proinflammatory cytokines induced by the administration of bacterial lipopolysaccharide. Destruction of terminal sensory nerve endings before lipopolysaccharide administration abrogates tachykinin synthesis and down-regulates TNF-α transcription and secretion. In contrast, the responses of interleukins-1 and -6 are unaffected. Pretreating animals with an antagonist for the substance P-specific NK-1 receptor also down-regulated the TNF-α response, whereas blockade of the NK-2 receptor had no effect. These findings indicate that substance P contributes to the induction of those cytokines that are involved in precipitating the shock response.

Original languageEnglish (US)
Pages (from-to)602-605
Number of pages4
JournalJournal of Leukocyte Biology
Volume63
Issue number5
DOIs
StatePublished - May 1998

Keywords

  • Inflammation
  • Shock
  • Tachykinins
  • Tumor necrosis factor α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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