Corticosteroid modulated immune activation in the TB immune reconstitution inflammatory syndrome

G. Meintjes, K.H. Skolimowska, K.A. Wilkinson, K. Matthews, R. Tadokera, A. Conesa Botella, R. Seldon, M.X. Rangaka, K. Rebe, D.J. Pepper, C. Morroni, R. Colebunders, G. Maartens, R.J. Wilkinson

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    RATIONALE: HIV-tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an immunopathological reaction to mycobacterial antigens induced by antiretroviral therapy (ART). Prednisone reduces morbidity in TB-IRIS, but the mechanisms are unclear. OBJECTIVES: To determine the effect of prednisone on the inflammatory response in TB-IRIS (antigen-specific effector T cells, cytokines and chemokines). METHODS: Samples were taken from participants in a randomized placebo-controlled trial of prednisone for TB-IRIS, at 0, 2 and 4 weeks. Participants received prednisone at a dose of 1.5mg/kg/day for 2 weeks followed by 0.75mg/kg/day for 2 weeks, or identical placebo. MEASUREMENTS: Interferon gamma ELISpot. RT-PCR on PBMC after restimulation with heat-killed Mycobacterium tuberculosis and Luminex multiplex cytokine analysis on corresponding tissue culture supernatants. Luminex multiplex cytokine analysis of serum. MAIN RESULTS: 58 participants with TB-IRIS (31 prednisone, 27 placebo) were included. In serum, significant decreases in IL-6, IL-10, IL-12p40, TNFalpha, IFNgamma and IP-10 concentrations during prednisone, but not placebo, treatment were observed. No differences in ELISpot responses comparing prednisone and placebo groups were shown in response to ESAT-6, Acr1, Acr2, 38kDa or heat killed H37Rv M. tuberculosis. PPD ELISpot responses increased over 4 weeks in prednisone group and decreased in placebo group (p=0.007). CONCLUSIONS: The beneficial effects of prednisone in TB-IRIS appear mediated via suppression of predominantly pro-inflammatory cytokine responses of innate immune origin, not via a reduction of the numbers of antigen-specific T cells in peripheral blood.
    Original languageEnglish
    JournalAmerican Journal of Respiratory and Critical Care Medicine
    Volume186
    Issue number4
    Pages (from-to)369-377
    Number of pages9
    ISSN1073-449X
    DOIs
    Publication statusPublished - 2012

    Keywords

    • Viral diseases
    • HIV
    • AIDS
    • Co-infections
    • Bacterial diseases
    • Tuberculosis
    • Mycobacterium tuberculosis
    • IRIS
    • Immune reconstitution inflammatory syndrome
    • Immune activation
    • Corticosteroids
    • Inflammatory reactions
    • Prednisone
    • Serum
    • Concentration
    • Clinical trials
    • South Africa
    • Africa-Southern

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