title: Impaired production of cytokines is an independent predictor of mortality in HIV-1-infected patients.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Infectious Diseases, the Copenhagen Muscle Research Center, Rigshospitalet, Copenhagen, Denmark. sis@dadlnet.dk
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016207:Cytokines / Q000096:biosynthesis*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000401:mortality; D015497:HIV-1; D006801:Humans; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology*; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012044:Regression Analysis; D016019:Survival Analysis; D019562:Viral Load
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides