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Published ahead of print on January 18, 2005, doi:10.1164/rccm.200407-857OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 8, April 2005, 850-857

A more recent version of this article appeared on April 15, 2005
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Submitted on July 7, 2004
Accepted on January 12, 2005

Characterization of Cytokine and Chemokine Profiles of Severe Acute Respiratory Syndrome

Yong Jiang1*, Jun Xu2, Chengzhi Zhou2, Zhenguo Wu3, Shuqing Zhong2, Jinghua Liu1, Wei Luo2, Tao Chen2, Qinghe Qin1, and Peng Deng1

1 Department of Pathophysiology, Southern Medical University, Key Laboratory of Functional Proteomics of Guangdong Province, Guangzhou, Guangdong, China, 2 Guangzhou Institute of Respiratory Diseases, Guangzhou Medical College, Guangzhou, Guangdong, China, 3 Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong, Special Administrative Region, China

* To whom correspondence should be addressed. E-mail: yjiang{at}fimmu.com.

Rationale: There is currently no optimal treatment or effective drug for severe acute respiratory syndrome (SARS) due to a poor understanding of the immunopathological mechanism. 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 SARS patients were dynamically screened using a bead-based multi-assay system. Reverse-transcription PCR was performed for amplifying the messenger RNA. Histopathology of the lung and lymphoid tissues of autopsy was examined using methods of immunohistochemistry and double immunofluorescent staining. Main Results: Interferon-inducible protein 10 (IP-10) elevated markedly in the blood at the early stage of SARS, and maintained 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 (IL-6), interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) were concomitantly increased in the blood of the patients with superinfection, and the mRNAs for these cytokines were also increased in the 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 following the immune injury is the main cause of death. The prompt elevation of IL-6, IL-8 and MCP1 is a sign of superinfection indicating a high risk of death.
Key words: severe acute respiratory syndrome, cytokine, chemokine, coronavirus




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