In vitro and in vivo induction of tumor necrosis factor alpha by Borrelia burgdorferi.
Tumor necrosis factor alpha (TNF-alpha) is an immunoregulatory cytokine with many biological activities including the mediation of inflammation. We examined sera and synovial fluids from patients seropositive for infection with Borrelia burgdorferi using a radioimmunoassay specific for TNF-alpha. Significant elevation of TNF-alpha was found in the sera and synovial fluids of patients examined, while controls showed no elevation. Sera of mice infected with B. burgdorferi contained elevated levels of TNF-alpha which varied during the course of a 24-day infection. To determine whether B. burgdorferi is capable of inducing TNF-alpha production, spirochetes were added to adherent human peripheral blood mononuclear cells or mouse peritoneal exudate cells and 24 h later supernatants were assayed. TNF-alpha induction occurred in a dose-dependent manner. The maximum stimulation occurred when a ratio of 1 to 10 spirochetes per mononuclear cell was used. At optimal concentrations, induction was not diminished by inactivation of spirochetes or pretreatment with polymyxin B. These results suggest that an increase in TNF-alpha production may occur as a result of infection with B. burgdorferi.
Defosse
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DL
Department of Microbiology, University of Minnesota, Minneapolis 55455.
Johnson
R C
RC
D000818:Animals; D015748:Borrelia burgdorferi Group / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000633:toxicity; D008193:Lyme Disease / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013582:Synovial Fluid / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha