The Role of Tumor Necrosis Factor in Host Defense against Scrub Typhus Rickettsiae. I. Inhibition of Growth ofRickettsia tsutsugamushi, Karp Strain, in Cultured Murine Embryonic Cells and Macrophages by Recombinant Tumor Necrosis Factor-Alpha

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Abstract
Recombinant murine tumor necrosis factor-alpha (TNF-alpha) inhibited intracellular growth of Rickettsia tsutsugamushi, Karp strain, in the mouse embryo cell line C3H/10T1/2 clone 8 at doses of 100 to 10 U/ml. The growth inhibitory effect of TNF-alpha was also evident when peritoneal exudate macrophages or bone marrow-derived macrophages were used as the host cell for rickettsial growth. Interferon-gamma (IFN-gamma), at doses up to 1,000 U/ml, did not affect the growth of this strain of rickettsiae in the mouse embryo cell line but, as expected, profoundly inhibited rickettsial growth in peritoneal exudate macrophages and bone marrow-derived macrophages. The effect of TNF-alpha on rickettsial growth in the mouse embryo cell line was not reproducibly enhanced by IFN-gamma. Treatment of the cell line with TNF-alpha delayed rickettsial cytopathic effects, but the rickettsiae ultimately grew to high numbers in the cells and caused cell death. These findings show that, at least in our system, R. tsutsugamushi is resistant to IFN-gamma-mediated antirickettsial effects in cells other than macrophages. The results of this study support the suggestion that TNF-alpha may inhibit rickettsial growth in cells other than macrophages.

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