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Implications of Dynamic Changes among Tumor Necrosis Factor- (TNF-), Membrane TNF Receptor, and Soluble TNF Receptor Levels in Regard to the Severity of Dengue Infection

Tumor necrosis factor- (TNF-) and soluble TNF receptors (sTNFR1 and sTNFR2) have been implicated in infectious diseases. We investigated dynamic changes among TNF-, membrane TNF receptors (mTNFR1 and mTNFR2), and sTNFR1 and sTNFR2 levels for patients with dengue hemorrhagic fever (DHF) and those not infected during a DEN-2 outbreak in southern Taiwan in 2002–2003. Patients with DHF showed the lowest levels of mTNFR1 and mTNFR2 expression. Multivariate analysis showed that a decrease in levels of mTNFR1 expression was the only factor significantly different between patients with DHF and those with dengue fever. Moreover, lower mTNFR1 expression was significantly correlated with higher plasma TNF- levels, but not with sTNFR1 levels in patients with DHF. This finding suggests that a lower level of mTNFR1 expression in response to a higher plasma TNF- level may be a pathogenic marker for early detection of DHF.

Received November 13, 2006. Accepted for publication May 1, 2007.

Acknowledgments: We thank Dr. Eng-Yen Huang for assistance with statistical analysis and M.S. Hau Chuang for technical assistance.

Financial support: This study was supported in part by grants NSC93-2314-B-182A-010 and NSC95-2314-B-182A-042-MY2 from the National Science Council, Taiwan.

^* Address correspondence to Kuender D. Yang, Department of Medical Research, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan, Republic of China. E-mail: yangkd{at}adm.cgmh.org.tw

Authors’ addresses: Lin Wang, Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan, Republic of China and Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan, Republic of China, Telephone: 886-7-731-7123 extension 8795, Fax: 886-7-733-8009, E-mail: wanglin{at}adm.cgmh.org.tw. Rong-Fu Chen, Department of Biological Sciences, National Sun Yatsen University, Kaohsiung, Taiwan, Republic of China, Telephone: 886-7-731-7123 extension 8857, Fax: 886-7-7312867. Jien-Wei Liu, Department of Internal Medicine, Division of Infectious Diseases, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan, Republic of China, Fax: 886-7-7320402. Hong-Ren Yu and Ho-Chang Kuo, Department of Pediatrics, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan, Republic of China, Telephone: 886-7-731-7123 extension 8848, Fax: 886-7-7312867. Kuender D. Yang, Departments of Pediatrics and Medical Research, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan, Republic of China.

Reprint requests: Kuender D. Yang, Department of Medical Research (12F12L), Chang Gung Memorial Hospital-Kaohsiung Medical Center, No. 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung 833, Taiwan, Republic of China, Telephone: 886-7-731-7123 extension 8848, Fax: 886-7-7312-867, E-mail: yangkd{at}adm.cgmh.org.tw.