In vitro and in vivo induction of tumor necrosis factor alpha by Borrelia burgdorferi

Abstract

Tumor necrosis factor alpha (TNF-α) 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-α. Significant elevation of TNF-α 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-α which varied during the course of a 24-day infection. To determine whether B. burgdorferi is capable of inducing TNF-α production, spirochetes were added to adherent human peripheral blood mononuclear cells or mouse peritoneal exudate cells and 24 h later supernatants were assayed. TNF-α 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-α production may occur as a result of infection with B. burgdorferi.