Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome


Tadokera, R; Meintjes, G; Skolimowska, KH; Wilkinson, KA; Matthews, K; Seldon, R; Chegou, NN; Maartens, G; Rangaka, MX; Rebe, K; Walzl, G; Wilkinson, RJ; (2011) Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome. The European respiratory journal, 37 (5). pp. 1248-1259. ISSN 0903-1936 DOI: https://doi.org/10.1183/09031936.00091010

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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)-1 beta, IL-5, IL-6, IL-10, IL-13, IL-17A, interferon (IFN)-gamma, 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-1 beta, IL-2, IL-6, IL-8, IL-10, IL-12p40, IFN-gamma, GM-CSF and TNF in TB-IRIS cultures. In serum, higher concentrations of TNF, IL-6, and IFN-gamma 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.

Item Type: Article
Keywords: HIV-1, immune reconstitution inflammatory syndrome, immunology, tuberculosis, ACTIVE ANTIRETROVIRAL THERAPY, NECROSIS-FACTOR-ALPHA, CO-INFECTED, PATIENTS, T-CELL RESPONSES, HIV-1-INFECTED PATIENTS, RESTORATION, SYNDROME, RISK-FACTORS, CASE-DEFINITION, CYTOKINE STORM, SOUTH-AFRICA
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 20817712
Web of Science ID: 290089200035
URI: http://researchonline.lshtm.ac.uk/id/eprint/730

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