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Int J Infect Dis. 2010 Apr;14(4):e328-33. doi: 10.1016/j.ijid.2009.06.002. Epub 2009 Aug 20.

Correlation between the concentrations of tumor necrosis factor-alpha and the severity of disease in patients infected with Orientia tsutsugamushi.

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First Department of Internal Medicine, Faculty of Medical Science, University of Fukui, Matsuoka, Fukui, Japan.



Patients with tsutsugamushi disease sometimes die if they do not receive appropriate chemotherapy. This study measured the concentration of several cytokines both before and after the administration of tetracyclines, and evaluated the changes in cytokine levels in patient serum to investigate the relationship between serum levels of cytokines and disease severity.


A total of nine patients were infected with Orientia tsutsugamushi. The diagnosis of tsutsugamushi disease was made using an indirect immunoperoxidase antibody test. The serum concentrations of cytokines were measured using enzyme-linked immunosorbent assays.


The levels of interleukin (IL)-10 (mean 71.7 pg/ml) and IL-12p40 (mean 588 pg/ml) were elevated in all patients in the acute phase, above the normal upper limits. Tumor necrosis factor-alpha (TNF-alpha) levels (mean 9.20 pg/ml) were elevated in 89% and interferon-gamma (IFN-gamma) levels (mean 41.0 pg/ml) in 44% of patients. The down-regulation of these overproduced cytokines was observed after chemotherapy. There was a significant correlation between the concentrations of TNF-alpha in the acute phase and the severity of disease (r=0.918).


The concentration of TNF-alpha may predict the severity of tsutsugamushi disease in the acute infectious phase.

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