title: Role of the interleukin 10 family of cytokines in patients with immune reconstitution inflammatory syndrome associated with HIV infection and tuberculosis.
abstract: BACKGROUND
  The interleukin 10 (IL-10) family comprises cytokines structurally related to IL-10 that share signaling receptors that have conserved signaling cascades. The immunopathogenesis of immune reconstitution inflammatory syndrome (IRIS) in patients with human immunodeficiency virus (HIV) infection and tuberculosis remains incompletely understood. We hypothesized that a deficiency of IL-10 and its homologs may contribute to the immunopathology of IRIS in these patients.
  
  
  METHODS
  We performed a case-control analysis involving patients with HIV infection and tuberculosis who had IRIS at clinical presentation (tuberculosis-IRIS) and similar patients with HIV infection and tuberculosis who did not develop tuberculosis-IRIS (non-IRIS). Peripheral blood mononuclear cells (PBMCs) were cultured in the presence or absence of heat-killed Mycobacterium tuberculosis for 6 and 24 hours. Messenger RNA was analyzed by quantitative reverse transcription polymerase chain reaction analysis. Cytokine concentrations in serum were also determined.
  
  
  RESULTS
  Cultures of PBMCs stimulated with M. tuberculosis for 24 hours yielded higher IL-10 and interleukin 22 (IL-22) transcript levels for tuberculosis-IRIS patients, compared with non-IRIS patients. Analysis of corresponding serum samples showed significantly higher concentrations of IL-10 and IL-22 in tuberculosis-IRIS patients, compared with non-IRIS patients.
  
  
  CONCLUSIONS
  IL-10 and IL-22 were differentially induced in PBMCs from tuberculosis-IRIS patients after in vitro stimulation, and higher concentrations of their corresponding proteins were detected in serum (in vivo). The higher levels of IL-10 observed in this study may represent a compensatory antiinflammatory response during tuberculosis-IRIS. The elevated levels of IL-22 suggest an association between this cytokine and immunopathology during tuberculosis-IRIS.
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tadokera
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Graeme A
authors.initials: GA
authors.lastname: Meintjes
authors.forename: Keira H
authors.initials: KH
authors.lastname: Skolimowska
authors.forename: Kerryn
authors.initials: K
authors.lastname: Matthews
authors.forename: Ronnett
authors.initials: R
authors.lastname: Seldon
authors.forename: Molebogeng X
authors.initials: MX
authors.lastname: Rangaka
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D005260:Female; D006678:HIV / Q000276:immunology / Q000472:pathogenicity*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000276:immunology / Q000382:microbiology / Q000473:pathology* / Q000821:virology; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000097:blood / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014376:Tuberculosis / Q000276:immunology / Q000473:pathology*; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D016753:Interleukin-10; D007378:Interleukins; D012333:RNA, Messenger; D000097043:Interleukin-22; C508609:IL10 protein, human