Macrophage‐Activating Cytokines in Human Immununodeficiency Virus Type 1–Infected and –Uninfected Patients with Pulmonary Tuberculosis

Abstract

Tuberculosis (TB) is the most common opportunistic infection in human immunodeficiency virus type 1 (HIV-1)-infected patients globally and occurs throughout the course of HIV-1 disease. Here the production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha by peripheral blood mononuclear cells (PBMC) of HIV-1-infected versus -uninfected patients with newly diagnosed pulmonary TB (PTB) was compared. Findings were correlated with cytokine profiles, clinical presentation, and expression of inducible nitric oxide (iNOS). Most HIV-1/PTB patients with a CD4 cell count of 200-500 cells/microL had high IFN-gamma production and radiographic evidence of atypical PTB. Low IFN-gamma production and radiographic evidence of reactivated PTB characterized both HIV-1/PTB patients with a CD4 cell count >or=500 cells/microL and HIV-1-uninfected patients. TNF-alpha levels were similar in all HIV-1/PTB patients, regardless of CD4 cell count. Induction of iNOS in PBMC was low and was associated with low IFN-gamma production. These data underscore the potential pathogenic role of macrophage-activating cytokines in TB in HIV-1-infected patients.

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

“…In contrast, although IL-18 production by PBMCs was not significantly different between the HIVpositive and HIV-negative TB patients, plasma IL-18 levels were higher in individuals with dual infection compared with those with TB alone. Mayanja-Kizza et al (20) studied in vivo levels of IL-12 and IL-18 in HIV-infected and uninfected patients with TB and reported findings similar to ours.…”

Cytokine responses induced by Mycobacterium tuberculosis in patients with HIV-1 infection and tuberculosis

“…Mayanja-Kizza et al showed that there was a marked variability in M. tuberculosis-stimulated IFN-g production in HIV patients with tuberculosis and that this was related to the degree of immunodeficiency. 6 Several studies have reported a low level of IFN-g production in HIV patients with tuberculosis, but the majority of these studies examined the dually infected patients as a group, regardless of individual CD4 cell status, 9,10 or the patients enrolled had severe tuberculosis, with frequent extrapulmonary dissemination. 11 Sodhi et al reported that the radiographic extent of disease and the site of disease were the only independent predictors of IFN-g production in HIV-negative and in HIV-infected patients, suggesting that reduced IFN-g production by PBMCs is a marker of severe tuberculosis regardless of HIV seropositivity.…”

“…5 Understanding the biology of IFN-g production and responsiveness among HIV-1 infected patients with TB (HIV/TB) is important because this cytokine may have a predominant protective role in TB infection, and it is emerging as a possible immunotherapeutic agent for patients with hard-to-treat TB. 3,6 In addition, the cellular production of TNF-a may be particularly important, as this cytokine is produced in response to mycobacterial products, is synthesized at elevated levels in active tuberculosis, and is important in granuloma formation. 4 Host immune responses to TB during its development in HIV patients, especially during highly active antiretroviral treatment (HAART), are not fully understood.…”

Activation of β‐Chemokines and CCR5 in Persons Infected with Human Immunodeficiency Virus Type 1 and Tuberculosis

“…HIV-1/PTB and PTB patients were recruited from the National Tuberculosis Control Programme clinic at Mulago Hospital in Kampala, Uganda. Eligibility criteria for patient enrollment were as noted in [14], which accompanies this report. In total, 67 HIV-1/PTB and 57 PTB patients were enrolled.…”