A probable role for IFN-gamma in the development of a lung immunopathology in SARS.
Recent work carried out in our laboratory showed the existence of a cytokine storm in SARS patients, dominated by Th1-type mediators. We thus hypothesized that IFN-gamma may play a major role in the pathology by triggering immune-mediated alveolar damage. As we assessed or re-assessed some effects of IFN-gamma on a number of human lung epithelial and fibroblast cell lines, chosen for their wide use in the literature, we found that alveolar epithelial cells were more sensitive to IFN-gamma, in terms of proliferation inhibition and enhancement of Fas-mediated apoptosis. While similar effects were obtained on fibroblasts, concentrations of IFN-gamma 4--8-fold greater were required. In addition, both epithelial and fibroblastic cell lines were able to secrete large quantities of T cell-targeting chemokines, similar to the ones detected in SARS patients. Based on the clinical data collected previously, the available literature and our in vitro experimentation, we propose that IFN-gamma may be responsible for acute lung injury in the late phase of the SARS pathology.
Theron
Michel
M
Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 701, Taiwan.
Huang
Kao-Jean
KJ
Chen
Yu-Wen
YW
Liu
Ching-Chuan
CC
Lei
Huan-Yao
HY
D017209:Apoptosis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002453:Cell Cycle / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017934:Coronavirus / Q000276:immunology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D019169:Jurkat Cells; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D006131:Growth Inhibitors; D019014:fas Receptor; D007371:Interferon-gamma