Impaired production of cytokines is an independent predictor of mortality in HIV-1-infected patients

OBJECTIVES: With regard to the natural history of HIV-1 infection this study investigated whether whole-blood culture cytokine production was associated with mortality in HIV-1-infected patients.

DESIGN AND METHODS: One hundred and seven HIV-1-infected patients stratified according to the Centers for Disease Control and Prevention criteria and 65 controls participated. The 24-h phytohaemagglutinin and lipopolysaccharide-stimulated whole-blood culture production of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL) receptor antagonist (-ra), IL-1beta, IL-12, IL-10, IL-2 and soluble (s) IL-2 receptor (-r)alpha were studied and progression was evaluated using Kaplan-Meier method and Cox proportional-hazards models.

RESULTS: Compared with controls, asymptomatic patients had increased production of IL-1beta and IL-12 (both P< 0.05), unchanged production of TNF-alpha, IFN-gamma and IL-1ra and notably reduced production of IL-10, IL-2 and sIL2-ralpha (all P< 0.05). HIV progression led to a progressive decline in whole-blood culture production of TNF-alpha, IFN-gamma, IL-1ra, IL-1beta, IL-12, IL-10 and IL-2 (all P< 0.0001). Low production of these cytokines were all associated with increased mortality risk in the patients (log-rank test, all P < 0.01, univariate Cox, all P< 0.001). Furthermore, low production of TNF-alpha, IL-1beta, IL-12 and IL-10 independently predicted mortality after adjusting for other known prognostic variables (multivariate Cox, all P< 0.05).

CONCLUSIONS: Preserved capacity of blood cells to produce cytokines was associated with prolonged survival in HIV-1-infected patients indicating a clinical significance of impaired cytokine production in HIV-1 infection.