Interferon-gamma and tumor necrosis factor-alpha exert their antirickettsial effect via induction of synthesis of nitric oxide. |
| |
| Authors: | H. M. Feng and D. H. Walker |
| |
| Affiliation: | Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609. |
| |
| Abstract: | How the host defenses control rickettsiae in the cytosol of nonphagocytic host cells, where they are not exposed to antibodies or phagocytes, has posed a difficult question. Rickettsia conorii infection of a mouse fibroblast cell line was inhibited in a dose-dependent manner by nitrogen oxide synthesized by eukaryotic host cells stimulated by interferon-gamma or tumor necrosis factor-alpha. L-arginine was the source of the nitric oxide as demonstrated by competitive inhibition by NG-monomethyl-L-arginine. Nitric oxide synthesis required host cell protein synthesis and had an approximately 48-hour lag phase following cytokine stimulation. At low doses of interferon-gamma and tumor necrosis factor-alpha, which had no detectable response as single agents, dramatic synergistic nitric oxide synthesis and antirickettsial effects were observed. |
| |
| Keywords: | |
|
|
