HIV Alters Plasma and<i>M. tuberculosis</i>-induced Cytokine Production in Patients with Tuberculosis

Subramanyam, Sudha; Hanna, Luke Elizabeth; Venkatesan, P; Sankaran, K; Narayanan, P. R.; Swaminathan, Soumya

doi:10.1089/107999004322813345

Cited by 24 publications

(20 citation statements)

References 22 publications

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“…HIV alters plasma and M. tuberculosis -induced cytokine production in patients with tuberculosis and this has been associated with reduced IFN-γ level in HIV patients coinfected with TB 33. This is consistent with our finding.…”

Section: Discussionsupporting

confidence: 92%

Interferon-gamma treatment kinetics among patients with active pulmonary tuberculosis

et al. 2013

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Introduction:Interferon-γ (IFN-γ) is essential for defence against Mycobacterium tuberculosis; however, levels in patients with active tuberculosis (TB) and changes during treatment have not been documented in our tuberculosis patients in Nigeria, hence this study has been carried out.Objective:To determine variations, treatment kinetics, and predictive value of IFN-γ levels during treatment of active tuberculosis.Design:Patients with pulmonary tuberculosis were recruited and subsequently followed up for 3 months during treatment with anti-TB. Peripheral blood was collected for IFN-γ assays, C-reactive protein and others followed by a Mantoux test. IFN-γ levels produced by stimulation with TB antigens were determined by ELISA and repeated measurement of IFN-γ were done at 1 and 3 months of anti-TB therapy. Chi Associations and correlations between IFN-γ were determined. Regression analysis was done to determine association between serial IFN-γ and treatment outcome.Results:We recruited 47 patients with active tuberculosis with a mean age of 34.8 ± 3.6 years and M:F ratio of 1.12:1. Six (11%) were HIV positive. The mean level of IFN-γ induced by TB antigens was 629 ± 114.1 pg/ml, higher for HIV-negative PTB patients compared with HIV-positive PTB patients, 609.78 ± 723.9 pg/ml and 87.88 ± 130.0 pg/ml, respectively, P-value = 0.000. The mean level of IFN-γ induced by TB antigen increased significantly from 629 ± 114.1 pg/ml to 1023.46 + 222.8 pg/ml, P-value = 0.03 and reduced to 272.3 ± 87.7 pg/ml by the third month on anti-TB drugs, P-value = 0.001. Negative correlation was observed between the mean of baseline and chest X-ray involvement, P = 0.03. There was no significant correlation between sputum smear grade with baseline and follow-up IFN-γ levels. Three-month IFN-γ level among cured patients were higher than those with treatment failure, regression analysis showed that it does not predict outcome.Conclusion:IFN-γ may be useful in early detection and monitoring response; however, large scale studies are needed.

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Section: Discussionsupporting

confidence: 92%

Interferon-gamma treatment kinetics among patients with active pulmonary tuberculosis

et al. 2013

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“…One of the studies revealed that the PBMCs of HIV-TB patients secrete less of IFN-γ and IL-12 when compared to TB patients after stimulation with mycobacterial antigens. However, these in vitro observations did not correlate with in vivo observations where higher levels of IFN-γ, IL-12 and IL-18 were detected in the plasma of HIV-TB patients [9], suggesting that the in vitro stimulation assays cannot be taken as a reflection of the response to HIV and TB infections under systemic conditions. Several studies have provided clues for the population variations in the cytokine responses [10].…”

Section: Introductionmentioning

confidence: 61%

Discordance in CD4+T-Cell Levels and Viral Loads with Co-Occurrence of Elevated Peripheral TNF-α and IL-4 in Newly Diagnosed HIV-TB Co-Infected Cases

et al. 2013

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BackgroundCytokines are the hallmark of immune response to different pathogens and often dictate the disease outcome. HIV infection and tuberculosis (TB) are more destructive when confronted together than either alone. Clinical data related to the immune status of HIV-TB patients before the initiation of any drug therapy is not well documented. This study aimed to collect the baseline information pertaining to the immune status of HIV-TB co-infected patients and correlate the same with CD4+T cell levels and viral loads at the time of diagnosis prior to any drug therapy.Methodology/Principal FindingsWe analyzed the cytokines, CD4+T cell levels and viral loads to determine the immune environment in HIV-TB co-infection. The study involved four categories namely, Healthy controls (n = 57), TB infected (n = 57), HIV infected (n = 59) and HIV-TB co-infected (n = 57) patients. The multi-partite comparison and correlation between cytokines, CD4+T-cell levels and viral loads prior to drug therapy, showed an altered TH1 and TH2 response, as indicated by the cytokine profiles and skewed IFN-γ/IL-10 ratio. Inadequate CD4+T cell counts in HIV-TB patients did not correlate with high viral loads and vice-versa. When compared to HIV category, 34% of HIV-TB patients had concurrent high plasma levels of IL-4 and TNF-α at the time of diagnosis. TB relapse was observed in 5 of these HIV-TB co-infected patients who also displayed high IFN-γ/IL-10 ratio.Conclusion/SignificanceWith these studies, we infer (i) CD4+T-cell levels as baseline criteria to report the disease progression in terms of viral load in HIV-TB co-infected patients can be misleading and (ii) co-occurrence of high TNF-α and IL-4 levels along with a high ratio of IFN-γ/IL-10, prior to drug therapy, may increase the susceptibility of HIV-TB co-infected patients to hyper-inflammation and TB relapse.

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“…We found increased IFN-γ expression in necrotic granulomas and, although, like TNF-α, it is crucial in defence against Mtb , high effector cytokine levels during chronic phases of disease may contribute to immunopathology, especially in the presence of high TNF-α expression [54], [36], [53]. The strong correlation between TNF-α and IFN-γ expression and HIV positivity supports the concept that cytokine overproduction may represent an attempt to compensate for the failure of other CD4 effector T cell functions, including proper granuloma formation and the antigen-specific activation of macrophages [19], [55], [53].…”

Section: Discussionmentioning

confidence: 99%

Pleural Tuberculosis in Patients with Early HIV Infection Is Associated with Increased TNF-Alpha Expression and Necrosis in Granulomas

et al. 2009

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Although granulomas may be an essential host response against persistent antigens, they are also associated with immunopathology. We investigated whether HIV co-infection affects histopathological appearance and cytokine profiles of pleural granulomas in patients with active pleural tuberculosis (TB). Granulomas were investigated in pleural biopsies from HIV positive and negative TB pleuritis patients. Granulomas were characterised as necrotic or non-necrotic, graded histologically and investigated for the mRNA expression of IL-12, IFN-γ, TNF-α and IL-4 by in situ hybridisation. In all TB patients a mixed Th1/Th2 profile was noted. Necrotic granulomas were more evident in HIV positive patients with a clear association between TNF-α and necrosis. This study demonstrates immune dysregulation which may include TNF-α-mediated immunopathology at the site of disease in HIV infected pleural TB patients.

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HIV Alters Plasma andM. tuberculosis-induced Cytokine Production in Patients with Tuberculosis

Cited by 24 publications

References 22 publications

Interferon-gamma treatment kinetics among patients with active pulmonary tuberculosis

Interferon-gamma treatment kinetics among patients with active pulmonary tuberculosis

Discordance in CD4+T-Cell Levels and Viral Loads with Co-Occurrence of Elevated Peripheral TNF-α and IL-4 in Newly Diagnosed HIV-TB Co-Infected Cases

Pleural Tuberculosis in Patients with Early HIV Infection Is Associated with Increased TNF-Alpha Expression and Necrosis in Granulomas

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