Differential TNF-a Responses during Hospital Treatment in Patients with Scrub Typhus

초록

Tumor necrosis factor- (TNF-) is a major pro-inflammatory cytokine and essential for host resistance against infection. It causes recruitment and activation of neutrophil at the site of infection and activates macrophages against various intracellular pathogens. TNF- was found to be produced by macrophages in response to the heat-stable molecules of O. tsutsugamushi and demonstrated to inhibit the intracellular growth of O. tsutsugamushi in the mouse embryo cell line and peritoneal macrophages. In contrast to these beneficial effects for defense against pathogens, the inflammatory response of TNF- could leads to harmful, or even fatal, consequences, as seen in septic shock or multiple organ failure. In human studies, several conflicting results have been reported on the kinetics of TNF- response during antibiotic treatment of patient. It has been reported that significant increases in levels of TNF- were observed during the convalescent phase in five patients, and they exceeded the levels observed during the acute phase. This result is somewhat unexpected considering that the patients received antibiotic treatment and recovered into convalescent phase. Therefore, there might be some differential kinetics of TNF-response among patients that is contributed to bacterial strain or patient’s immune status. In this study, we studied the changes of serum levels of TNF- IL-10, and IL-12 during antibiotic treatment of scrub typhus. Although the levels of these cytokines have general tendency to decrease, the serum levels of TNF-, in selected patients, continue to increase during antibiotic treatment. This finding is surprising because antibiotic treatments are supposed to reduce the bacterial burden causing release of inflammatory cytokines and doxycycline has suppressing effect on cytokine production. We recently reported that O. tsutsugamushi induce IL-10 in mice, which