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Volume 16, Number 11, Issue of June 1, 1996 pp. 3745-3752
Copyright ©1996 Society for Neuroscience

Endogenous Substance P Mediates Cold Water Stress-Induced Increase in Interleukin-6 Secretion from Peritoneal Macrophages

Received Nov. 21, 1995; revised Feb. 5, 1996; accepted March 6, 1996.

Goafa F. Zhu¹, Cheryl Chancellor-Freeland¹, Ari S. Berman¹, Reinhard Kage², Susan E. Leeman², David I. Beller³, and Paul H. Black¹

Departments of ¹ Microbiology, ² Pharmacology, and ³ Medicine, Boston University School of Medicine, Boston, Massachusetts 02118

Previous studies from this laboratory had shown that exposure of mice to cold water stress leads to an increase in the secretion of interleukin-1 (IL-1) and tumor necrosis factor- (TNF) from their peritoneal macrophages. We now report that the secretion of IL-6 from peritoneal macrophages is also increased after cold water stress and that the peptide substance P (SP) participates in this stress-induced response. The stress paradigm involved subjecting male C57BL/6J mice to 5 min swim tests in 10 ± 2°C water twice daily for 4 d. Cold water stress augments the lipopolysaccharide-induced IL-6 secretion from peritoneal macrophages, elevates immunoreactive SP (iSP) in the peritoneal wash fluid, and reduces iSP in certain peritoneum-containing tissues or organs (i.e., diaphragm, abdominal wall, ileum, and rectum). The 10 d stress time course studies indicate that increased IL-6 secretion is positively related to elevated iSP in the peritoneal wash fluid and inversely related to reduced iSP in certain peritoneum-containing tissues. Pretreatment with capsaicin, which depletes SP in the sensory nerve endings, eliminates stress-control differences in the peritoneal wash fluid and in certain peritoneal tissues. Moreover, RP67,580, a specific SP antagonist, eliminates the cold water stress-induced augmentation of IL-6 secretion from peritoneal macrophages. These results suggest that cold water stress promotes the release of SP from peritoneal tissues into the peritoneal cavity, where it participates in the cold water stress-induced macrophage functional alterations.

Key words: substance P; stress; macrophage; cytokine; interleukin-6; capsaicin; RP67,580

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