Immunoregulation by macrophages. III. Prostaglandin E suppresses lymphocyte activation but not macrophage effector function during Salmonella enteritidis infection.
Peritoneal macrophages obtained during primary or secondary infection with Salmonella enteritidis differ in the proportions of subpopulations with the capacity to secrete prostaglandin E (PGE) and interleukin 1 (IL1) and have bactericidal and tumoricidal activities in vitro. Using indomethacin in vivo and PGE in vitro we have studied the regulation of subpopulations of lymphocytes and macrophages by PGE during the inflammatory reaction. Indomethacin treatment promoted clearance of the Salmonella and a 50-90% increase in macrophages recovered from the peritoneal cavity in both primary and secondary infected animals. Whilst blocking the capacity of macrophages to secrete PGE in vitro the indomethacin treatment did not alter their bactericidal (or tumoricidal) activity nor their cyclic AMP response to PGE2. A major effect of indomethacin in vivo and of PGE2 in vitro however, was on the production and expression of IL1 and IL2. Secretion of IL1 by macrophages in vitro was greatly enhanced in indomethacin treated mice and was suppressed in vitro by PGE2. Prostaglandin E2 also inhibited IL1 dependent T-lymphocyte differentiation. IL2 secretion and IL2 dependent blast cell proliferation in vitro and sensitivity of the cells to PGE2 inhibition increased through this sequence of reactions. Lymphocyte populations harvested at intervals during primary or secondary infection differed in their cyclic AMP response to PGE2 and in IL2 secretion in vitro. This may be related to changes in the proportions of lymphocyte subsets having Lyt 1+ markers. We conclude that peritoneal macrophages from Salmonella infected mice differ in their capacity to secrete PGE and IL1.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology / Q000382:microbiology; D003114:Colony-Forming Units Assay; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D011458:Prostaglandins E / Q000276:immunology* / Q000494:pharmacology*; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology; D012477:Salmonella enteritidis; D013601:T-Lymphocytes / Q000276:immunology
D007375:Interleukin-1; D007376:Interleukin-2; D011458:Prostaglandins E; D000242:Cyclic AMP; D015232:Dinoprostone; D007213:Indomethacin