Early Enhanced Expression of Interferon-Inducible Protein-10 (CXCL-10) and Other Chemokines Predicts Adverse Outcome in Severe Acute Respiratory Syndrome

Abstract

Background: Exaggerated activation of cytokines/chemokines has been proposed as a factor in adverse outcome of severe acute respiratory syndrome (SARS). Previous studies on chemokines have included only small numbers of patients, and the utility of plasma chemokines as prognostic indicators is unclear. Methods: We studied 255 archival plasma samples collected during the first or second week after disease onset. The chemokines interferon-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and regulated upon activation normal T cell expressed and secreted (RANTES) were measured by cytometric bead array with a 4-color FACSCalibur flow cytometer. Reverse transcription and real-time quantitative PCR and immunohistochemical staining were performed to analyze the production of IP-10 in lung tissue at autopsy. Conditional logistic regression was used to identify independent predictors for adverse disease outcome. Results: Increases in IP-10, MIG, and IL-8 during the first week after onset of fever were associated with adverse outcome (intensive care unit admission or death) in the univariate analysis. During the second week, only MIG concentration was associated with prognosis. After adjusting for other risk factors, plasma IP-10 concentration at the first week remained as an independent prognostic factor, with an odds ratio for adverse outcome of 1.52 (95% confidence interval, 1.05–2.55) per fold increase in plasma IP-10 concentration above the median. During the second week, chemokines provided little independent prognostic information. IP-10 was increased in lung tissue from patients who died of SARS. Conclusions: Increased plasma IP-10 during the first week of SARS symptoms is an independent predictor of outcome. Chemokine activation may be an early event in SARS, and an exaggerated host response may produce complications.