title: Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome.
abstract: Increased access to combination antiretroviral therapy in areas co-endemic for tuberculosis (TB) and HIV-1 infection is associated with an increased incidence of immune reconstitution inflammatory syndrome (TB-IRIS) whose cause is poorly understood. A case-control analysis of pro- and anti-inflammatory cytokines in TB-IRIS patients sampled at clinical presentation, and similar control patients with HIV-TB prescribed combined antiretroviral therapy who did not develop TB-IRIS. Peripheral blood mononuclear cells were cultured in the presence or absence of heat-killed Mycobacterium tuberculosis for 6 and 24 h. Stimulation with M. tuberculosis increased the abundance of many cytokine transcripts with interleukin (IL)-1β, IL-5, IL-6, IL-10, IL-13, IL-17A, interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor (TNF) being greater in stimulated TB-IRIS cultures. Analysis of the corresponding proteins in culture supernatants, revealed increased IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p40, IFN-γ, GM-CSF and TNF in TB-IRIS cultures. In serum, higher concentrations of TNF, IL-6, and IFN-γ were observed in TB-IRIS patients. Serum IL-6 and TNF decreased during prednisone therapy in TB-IRIS patients. These data suggest that cytokine release contributes to pathology in TB-IRIS. IL-6 and TNF were consistently elevated and decreased in serum during corticosteroid therapy. Specific blockade of these cytokines may be rational approach to immunomodulation in TB-IRIS.
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Tadokera
authors.forename: G
authors.initials: G
authors.lastname: Meintjes
authors.forename: K H
authors.initials: KH
authors.lastname: Skolimowska
authors.forename: K A
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: K
authors.initials: K
authors.lastname: Matthews
authors.forename: R
authors.initials: R
authors.lastname: Seldon
authors.forename: N N
authors.initials: NN
authors.lastname: Chegou
authors.forename: G
authors.initials: G
authors.lastname: Maartens
authors.forename: M X
authors.initials: MX
authors.lastname: Rangaka
authors.forename: K
authors.initials: K
authors.lastname: Rebe
authors.forename: G
authors.initials: G
authors.lastname: Walzl
authors.forename: R J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011241:Prednisone / Q000627:therapeutic use; D014376:Tuberculosis / Q000097:blood / Q000276:immunology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D011241:Prednisone
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