Tumor Necrosis Factor-α Plays a Role in Host Defense against Histoplasma capsulatum

Tumor necrosis factor-a was detected in supematants collected from BALB/c mouse peritoneal macrophages incubated continuously with Histoplasma capsulatum. The levels of TNFa measured by actinomycin D bioassay peaked within hours after exposure and then greatly declined by 24 h. TNFa was also measured in bronchoalveolar lavage fluid from BALB/c mice challenged intranasally with H. capsulatum. Lavage fluid TNFa levels exhibited the same pattern as the in vitro supematants; they peaked within hours after challenge and lower levels were detected at 24 h. Treatment of mice with anti-TNFa antibody accelerated mortality in response to systemic infection and significantly increased tissue colony counts in the liver and spleen. In the murine model, TNFa is produced in response to H. capsulatum and appears to play some role in host defense to infection.