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Published ahead of print on January 18, 2005, doi:10.1164/rccm.200407-857OC
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American Journal of Respiratory and Critical Care Medicine Vol 171. pp. 850-857, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200407-857OC

Original Article

Characterization of Cytokine/Chemokine Profiles of Severe Acute Respiratory Syndrome

Yong Jiang*, Jun Xu*, Chengzhi Zhou, Zhenguo Wu, Shuqing Zhong, Jinghua Liu, Wei Luo, Tao Chen, Qinghe Qin and Peng Deng

Key Laboratory of Functional Proteomics of Guangdong Province, Department of Pathophysiology, Southern Medical University, and Guangzhou Institute of Respiratory Diseases, Guangzhou; and Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region, China

Correspondence and requests for reprints should be addressed to Yong Jiang, M.D., Ph.D., Department of Pathophysiology, Southern Medical University, Tonghe, Guangzhou 510515, China. E-mail: yjiang{at}fimmu.com; or Jun Xu, M.D., Ph.D., Guangzhou Institute of Respiratory Diseases, 151 Yanjiang Road, Guangzhou 510120, China. E-mail: xufeili{at}vip.163.com

Rationale: There is currently no optimal treatment or effective drug for severe acute respiratory syndrome (SARS), because the immunopathologic mechanism is poorly understood. Objectives: To explore the immune mechanism underlying the pathogenesis of SARS, we studied the expression profile of cytokines/chemokines in the blood and the immunopathology of the lung and lymphoid tissues. Methods: Fourteen cytokines/chemokines in the blood of 23 patients with SARS were dynamically screened, using a bead-based multiassay system. Reverse transcription-polymerase chain reaction was performed to amplify mRNA. Histopathology of the lung and lymphoid tissues at autopsy was examined, using methods of immunohistochemistry and double immunofluorescence staining. Main Results: Interferon-inducible protein-10 (IP-10) was markedly elevated in the blood during the early stage of SARS, and remained at a high level until convalescence. Moreover, IP-10 was highly expressed in both lung and lymphoid tissues, where monocyte-macrophage infiltration and depletion of lymphocytes were observed. The levels of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 were concomitantly increased in the blood of the patients with superinfection, and the mRNAs for these cytokines were also increased in lung tissues. Conclusions: Induction of IP-10 is a critical event in the initiation of immune-mediated acute lung injury and lymphocyte apoptosis during the development of SARS. Superinfection after the immune injury is the main cause of death. The prompt elevation of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 is a sign of superinfection, indicating a high risk of death.

Key Words: chemokine • coronavirus • cytokine • severe acute respiratory syndrome




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