ENDOGENOUS SUBSTANCE-P MEDIATES COLD-WATER STRESS-INDUCED INCREASE ININTERLEUKIN-6 SECRETION FROM PERITONEAL-MACROPHAGES

Previous studies from this laboratory had shown that exposure of mice to cold water stress leads to an increase in the secretion of interieu kin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha) from their pe ritoneal macrophages. We now report that the secretion of IL-6 from pe ritoneal macrophages is also increased after cold water stress and tha t the peptide substance P (SP) participates in this stress-induced res ponse. The stress paradigm involved subjecting male C57BL/6J mice to 5 min swim tests in 10 +/- 2 degrees C water twice daily for 4 d. Cold water stress augments the lipopolysaccharide-induced IL-6 secretion fr om peritoneal macrophages, elevates immunoreactive SP (iSP) in the per itoneal wash fluid, and reduces iSP in certain peritoneum-containing t issues or organs (i.e., diaphragm, abdominal wall, ileum, and rectum). The 10 d stress time course studies indicate that increased IL-6 secr etion is positively related to elevated iSP in the peritoneal wash flu id and inversely related to reduced iSP in certain peritoneum-containi ng tissues. Pretreatment with capsaicin, which depletes SP in the sens ory nerve endings, eliminates stress-control differences in the perito neal wash fluid and in certain peritoneal tissues. Moreover, RP67,580, a specific SP antagonist, eliminates the cold water stress-induced au gmentation of IL-6 secretion from peritoneal macrophages. These result s suggest that cold water stress promotes the release of SP from perit oneal tissues into the peritoneal cavity, where it participates in the cold water stress-induced macrophage functional alterations.