The effect of HIV infection and HAART on inflammatory biomarkers in a population-based cohort of women

Abstract

Objective HIV causes inflammation that can be at least partially corrected by HAART. To determine the qualitative and quantitative nature of cytokine perturbation, we compared cytokine patterns in three HIV clinical groups including HAART responders (HAART), untreated HIV non-controllers (NC), and HIV-uninfected (NEG). Methods Multiplex assays were used to measure 32 cytokines in a cross-sectional study of participants in the Women's Interagency HIV Study (WIHS). Participants from 3 groups were included: HAART (n=17), NC (n=14), and HIV NEG (n=17). Results Several cytokines and chemokines showed significant differences between NC and NEG participants, including elevated IP-10 and TNF-α and decreased IL-12(p40), IL-15, and FGF-2 in NC participants. Biomarker levels among HAART women more closely resembled the NEG, with the exception of TNF-α and FGF-2. Secondary analyses of the combined HAART and NC groups revealed that IP-10 showed a strong, positive correlation with viral load and negative correlation with CD4+ T cell counts. The growth factors VEGF, EGF, and FGF-2 all showed a positive correlation with increased CD4+ T cell counts. Conclusion Untreated, progressive HIV infection was associated with decreased serum levels of cytokines important in T cell homeostasis (IL-15) and T cell phenotype determination (IL-12), and increased levels of innate inflammatory mediators such as IP-10 and TNF-α. HAART was associated with cytokine profiles that more closely resembled those of HIV uninfected women. The distinctive pattern of cytokine levels in the 3 study groups may provide insights into HIV pathogenesis, and responses to therapy.

The Th1/Th2/Th17 cytokine profile of HIV-infected individuals: A multivariate cytokinomics approach

“…In another South African-based study INF-g, IL-6 and IL-10 were elevated in a group of HIV-infected individuals with immune reconstitution inflammatory syndrome [16]. IL-2 and IL-6 were key cytokines elevated in simian immunodeficiency virus-infected monkeys with encephalitis [12]. These examples supports IL-6 and IL-10 levels as having a role in the immune response against HIV infection and potentially also in monitoring disease progression.…”

“…Similar to Jansen et al [25], it seems that viral load is the driving force determining the extent of the immune response. Keating et al [12] also showed this influence of viral load on the extent of cytokine perturbation (cytokines were less altered when viremia was lowered through treatment).…”

“…Measuring cytokine alterations during HIV infection [11][12][13][14][15][16] and other pathological states [17][18][19][20][21] is increasingly being investigated for use in predicting disease progression.…”

Inhibition of HIV-1 enzymes, antioxidant and anti-inflammatory activities of Plectranthus barbatus

“…These results can also be linked to anti-HIV properties of this plant; low levels of IL-17A in HIV-1 infection is associated with non-progression (Yue et al, 2008). IL-17A along with other cytokines such as IL-2 and IL-6 are elevated during the different stages of HIV infection (Keating et al, 2011;Nixon and Landay, 2010;Worsley et al, 2010;Yue et al, 2008). Therefore lowering the production of this cytokines especially IL-17A could contribute to slow or nonprogression of HIV infection.…”

The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection

“…They can accelerate the immune response against the virus [17], while simultaneously, cytokine activity amplifies the population of target cells for HIV infection by activating CD4+ T-cells. In chronic HIV infection, elevated concentrations of proinflammatory cytokine TNF-α and its receptor TNF-RII indicate long-term inflammation in infected persons [18] and [19].…”