Tumor Necrosis Factor Alpha and Prostaglandin E₂ Production by Human Monocyte‐derived Macrophages Infected with Spotted Fever Group Rickettsiaea, b

Abstract

Infection of macrophages by intracellular parasites might modulate production of tumor necrosis factor (TNF) and prostaglandin E2 (PGE2), which, in turn, might have a profound effect on the outcome of the infection in vivo. In this study we examined in an in vitro system, the rickettsial yield in human monocyte-derived macrophages (MdM) and the PGE2 and TNF production by MdM infected with Rickettsia conorii RC, Casablanca strain) or Israeli spotted fever (ISF, G-212 strain). TNF and PGE2 were determined in the media of MdM infected with RC or ISF. TNF reached maximum levels 24 h post-infection and then declined, while PGE2 levels increased continuously during the infection up to 96 h post-infection. Addition of dexamethasone inhibited both TNF and PGE2 production and enhanced rickettsial yield in MdM. Inhibition of PGE2 production by indomethacin resulted in increased production of TNF from rickettsial-infected MdM, while addition of PGE2 caused partial inhibition of TNF production from infected MdM.

Tumor necrosis factor alpha, interleukin-1 alpha, interleukin-6, and prostaglandin E2 production in murine peritoneal macrophages infected with Ehrlichia risticii

“…Although E. risticii induced PGE2 production by macrophages, the amount was much less than that produced by uninfected cells in response to LPS or to R cononi (15). As for TNF-a production, preexposure of macrophages to E. risticii depressed PGE2 production by the macrophages in response to subsequent stimulation with LPS.…”

“…Other obligate intracellular bacteria such as Rickettsia and Chlamydia spp. are reported to induce production of inflammatory mediators such as tumor necrosis factor alpha (TNF-a), interleukin-1 (IL-1), and/or prostaglandins by macrophages (14,15,26,31). In this study, we examined whether E. risticii induces production of these inflammatory mediators by host macrophages and whether the production is modulated by lipopolysaccharide (LPS) or gamma interferon (IFN--y) in mouse peritoneal macrophages in vitro.…”

Depletion of gamma interferon and tumor necrosis factor alpha in mice with Rickettsia conorii-infected endothelium: impairment of rickettsicidal nitric oxide production resulting in fatal, overwhelming rickettsial disease

“…Numerous in vitro experiments have demonstrated that cytokines exert an antirickettsial effect that results in clearance of organisms from the cytoplasm of some of the infected cells (14,23,39). Gamma interferon (IFN--y) and tumor necrosis factor alpha (TNF-oL) are important mediators of this antirickettsial activity (9,15,16,24,25). These two cytokines are quite effective synergistically in the clearance of R. conorii from a murine fibroblast cell line through induction of the synthesis of nitric oxide (3).…”

Relationship of tumor necrosis factor alpha, the nitric oxide synthase pathway, and lipopolysaccharide to the killing of gamma interferon-treated macrophage-like RAW264.7 cells by Rickettsia prowazekii

“…We demonstrated that R. prowazekii induces mouse macrophagelike RAW264.7 cells to produce TNF-ox, and Manor and Sarov (16) induces the production of TNF-ox in human monocyte-derived macrophages. Since the production of TNF-o by RAW264.7 cells in response to R. prowazekii was independent of rickettsial viability, the stimulation may have been a response to rickettsial LPS (21-23).…”