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 hy macrophage-treponeme interaction, inhibited concanava1in 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).