期刊
EUROPEAN RESPIRATORY JOURNAL
卷 37, 期 5, 页码 1248-1259出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00091010
关键词
HIV-1; immune reconstitution inflammatory syndrome; immunology; tuberculosis
资金
- Wellcome Trust [084323, 081667, 088316, 084670, 083226]
- European Union [Sante/2006/105-061]
- European and Developing Countries Clinical Trials Partnership (EDCTP) [060613]
- MRC [MC_U117588499] Funding Source: UKRI
- Medical Research Council [MC_U117588499] Funding Source: researchfish
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.
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