PMID- 23303806 OWN - NLM STAT- MEDLINE DCOM- 20130418 LR - 20231213 IS - 1537-6613 (Electronic) IS - 0022-1899 (Print) IS - 0022-1899 (Linking) VI - 207 IP - 7 DP - 2013 Apr TI - Role of the interleukin 10 family of cytokines in patients with immune reconstitution inflammatory syndrome associated with HIV infection and tuberculosis. PG - 1148-56 LID - 10.1093/infdis/jit002 [doi] AB - 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. FAU - Tadokera, Rebecca AU - Tadokera R AD - Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. FAU - Wilkinson, Katalin A AU - Wilkinson KA FAU - Meintjes, Graeme A AU - Meintjes GA FAU - Skolimowska, Keira H AU - Skolimowska KH FAU - Matthews, Kerryn AU - Matthews K FAU - Seldon, Ronnett AU - Seldon R FAU - Rangaka, Molebogeng X AU - Rangaka MX FAU - Maartens, Gary AU - Maartens G FAU - Wilkinson, Robert J AU - Wilkinson RJ LA - eng GR - U1175.02.002.00014.01/MRC_/Medical Research Council/United Kingdom GR - 081667/WT_/Wellcome Trust/United Kingdom GR - 088316/Wellcome Trust/United Kingdom GR - 084323/Wellcome Trust/United Kingdom GR - MC_U117588499/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130109 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (IL10 protein, human) RN - 0 (Interleukins) RN - 0 (RNA, Messenger) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Adult MH - CD4 Lymphocyte Count MH - Case-Control Studies MH - Cells, Cultured MH - Cross-Sectional Studies MH - Female MH - HIV/immunology/*pathogenicity MH - HIV Infections/immunology/*pathology MH - Humans MH - Immune Reconstitution Inflammatory Syndrome/immunology/microbiology/*pathology/virology MH - Interleukin-10/blood/genetics/*immunology MH - Interleukins/blood/genetics/immunology MH - Leukocytes, Mononuclear/immunology/microbiology/virology MH - Male MH - Middle Aged MH - Mycobacterium tuberculosis/immunology/pathogenicity MH - RNA, Messenger/analysis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Time Factors MH - Tuberculosis/immunology/*pathology MH - Young Adult MH - Interleukin-22 PMC - PMC3583273 EDAT- 2013/01/11 06:00 MHDA- 2013/04/20 06:00 PMCR- 2013/01/09 CRDT- 2013/01/11 06:00 PHST- 2013/01/11 06:00 [entrez] PHST- 2013/01/11 06:00 [pubmed] PHST- 2013/04/20 06:00 [medline] PHST- 2013/01/09 00:00 [pmc-release] AID - jit002 [pii] AID - 10.1093/infdis/jit002 [doi] PST - ppublish SO - J Infect Dis. 2013 Apr;207(7):1148-56. doi: 10.1093/infdis/jit002. Epub 2013 Jan 9.