A probable role for IFN-γ in the development of a lung immunopathology in SARS

Theron, Michel; Huang, Kao-Jean; Chen, Yu-Wen; Liu, Ching-Chuan; Lei, Huan-Yao

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-γ may play a major role in the pathology by triggering immune-mediated alveolar damage. As we assessed or re-assessed some effects of IFN-γ 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-γ, in terms of proliferation inhibition and enhancement of Fas-mediated apoptosis. While similar effects were obtained on fibroblasts, concentrations of IFN-γ 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-γ may be responsible for acute lung injury in the late phase of the SARS pathology.