Prostaglandins in experimental syphilis: treponemes stimulate adherent spleen cells to secrete prostaglandin E2, and indomethacin upregulates immune functions.
Incubation of microorganisms with macrophages enhances the production of prostaglandin E2 (PGE2). Previous research had indicated that macrophages from syphilitic rabbits suppressed spleen cell synthesis of interleukin-2 (IL-2); this suppressive activity was reversed by indomethacin. Experiments were designed to further characterize the involvement of prostaglandins in immune processing. When Treponema pallidum was incubated with unfractionated spleen preparations, PGE2 production was accelerated, and within 24 h, pharmacologic concentrations of the prostaglandin were detected. When cytochalasin B was used to block phagocytosis, decreased levels of PGE2 were apparent. Commercial preparations of PGE2, in the range generated by macrophage-treponeme interaction, inhibited concanavalin A-induced IL-2 secretion by splenic cells. T. pallidum stimulated IL-1 production by adherent cells, and indomethacin markedly enhanced this effect. In vivo, indomethacin upregulated immune function. Two groups of rabbits were infected, and one was given daily injections of indomethacin for 18 days. Both groups were treated with penicillin to terminate infections. One week later, rabbits were challenged with viable organisms to determine their immune status. The indomethacin-treated group was more resistant to reinfection. In further research, indomethacin enhanced the immunogenicity of vaccine preparations containing heat-killed T. pallidum. Results are discussed in terms of the role of PGE2 as it impinges on immune functions involving macrophage activation (IL-1 production) and T lymphocyte activation (IL-2 production).
Fitzgerald
T J
TJ
Department of Medical Microbiology, School of Medicine, University of Minnesota, Duluth 55812.
Tomai
M A
MA
Trachte
G J
GJ
Rice
T
T
D000818:Animals; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D010587:Phagocytosis; D011817:Rabbits; D013154:Spleen / Q000276:immunology*; D014210:Treponema pallidum / Q000276:immunology*; D015854:Up-Regulation
D007375:Interleukin-1; D007376:Interleukin-2; D015232:Dinoprostone; D007213:Indomethacin