title: Plasma levels of cytokines and chemokines and the risk of mortality in HIV-infected individuals: a case-control analysis nested in a large clinical trial.
abstract: BACKGROUND
  All-cause mortality and serious non-AIDS events (SNAEs) in individuals with HIV-1 infection receiving antiretroviral therapy are associated with increased production of interleukin-6 which appears to be driven by monocyte/macrophage activation. Plasma levels of other cytokines or chemokines associated with immune activation might also be biomarkers of an increased risk of mortality and/or SNAEs.
  
  
  METHODS
  Baseline plasma samples from 142 participants enrolled into the Strategies for Management of Antiretroviral Therapy study, who subsequently died, and 284 matched controls, were assayed for levels of 15 cytokines and chemokines. Cytokine and chemokine levels were analysed individually and when grouped according to function (innate/proinflammatory response, cell trafficking and cell activation/proliferation) for their association with the risk of subsequent death.
  
  
  RESULTS
  Higher plasma levels of proinflammatory cytokines (interleukin-6 and tumour necrosis factor-α) were associated with an increased risk of all-cause mortality but in analyses adjusted for potential confounders, only the association with interleukin-6 persisted. Increased plasma levels of the chemokine CXCL8 were also associated with all-cause mortality independently of hepatitis C virus status but not when analyses were adjusted for all confounders. In contrast, higher plasma levels of cytokines mediating cell activation/proliferation were not associated with a higher mortality risk and exhibited a weak protective effect when analysed as a group.
  
  
  CONCLUSIONS
  Whereas plasma levels of interleukin-6 are the most informative biomarker of cytokine dysregulation associated with all-cause mortality in individuals with HIV-1 infection, assessment of plasma levels of CXCL8 might provide information about causes of mortality and possibly SNAEs.
authors.affiliation: aSchool of Pathology and Laboratory Medicine, University of Western Australia bDepartment of Clinical Immunology, Royal Perth Hospital and PathWest, Laboratory Medicine, Perth, Australia cResearch Department of Infection and Population Health, University College London, London, United Kingdom dHouston AIDS Research Team, Division of Infectious Diseases, The University of Texas Health Science Center at Houston, Houston, USA eHIV Clinic and Department of Respiratory Medicine, Royal Free Hospital, London, United Kingdom fKirby Institute, University of New South Wales, Sydney, Australia gDepartment of Immunology and Microbiology, Rush University Medical Center, Chicago, USA.
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Arduino
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.forename: Amit C
authors.initials: AC
authors.lastname: Achhra
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
mesh_terms: D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D008297:Male; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D016207:Cytokines