Abstract

BackgroundCytokines play an important role in controlling the homeostasis of the immune system and infection with Human Immunodeficiency virus (HIV) leads to deregulated production of both pro- and anti-inflammatory cytokines. This study was designed to determine the effects of HIV and Highly Active Antiretroviral Therapy (HAART) on the levels of pro-and anti-inflammatory cytokines in HIV infected subjects.MethodA total of 50 HIV infected and 50 HIV seronegative control participants were recruited for the study. The HIV infected subjects were recruited before commencement of antiretroviral therapy and were followed up for 12 months. Blood samples were collected at 3 different points: before initiation of therapy, 6 months into therapy and 12 months into therapy. Serum cytokines were analyzed using ELISA method while CD4+ T cells and viral load counts were measured using standard laboratory methods.ResultThe results showed that pro-inflammatory cytokines: Tumour necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6) and anti-inflammatory cytokines Interleukin-4 (IL-4), Interleukin-10 (IL-10) and Transforming growth factor-beta (TGF-β) were significantly elevated in HIV infected subjects before commencement of therapy compared to 6 months and 12 months into therapy (P < 0.01) and compared to control participants (P < 0.01). TNF-α, TGF-beta remained significantly elevated even after 12 months of therapy compared to control participants (P < 0.01), while IL-4, IL-6, and IL-10 showed no significant difference compared to control participants after 12 months of therapy (P > 0.05). INF-γ was significantly reduced before commencement of therapy and after 12 months of therapy compared to control participants (P < 0.05) respectively.ConclusionTNF-α and TGF-β remained significantly elevated even after 12 months of therapy, while IFN-γ remained significantly reduced after 12 months of therapy. Regulating these cytokines which were unresponsive to therapy could serve as a potential measure of therapy for HIV infected subjects. The positive effect of 12 months therapy on IL-4, IL-6 and IL-10 levels can be used to monitor disease prognosis during therapy especially in resource poor setting where regular viral load monitoring is unavailable.

Highlights

  • Cytokines can be classified as pro and anti-inflammatory and are considered important initiators and mediators of inflammation [1]

  • Result: The results showed that pro-inflammatory cytokines: Tumour necrosis factor-alpha (TNF-α), Interleukin-6 (IL6) and anti-inflammatory cytokines Interleukin-4 (IL-4), Interleukin-10 (IL-10) and Transforming growth factor-beta (TGF-β) were significantly elevated in Human Immunodeficiency virus (HIV) infected subjects before commencement of therapy compared to 6 months and 12 months into therapy (P < 0.01) and compared to control participants (P < 0.01)

  • IL-4 and IL-10 showed no significant difference after 1 year of Highly Active Antiretroviral Therapy (HAART) compared to levels in control participants (P > 0.05), while Tissue Growth Factor beta (TGF-β) remained significantly high in HIV infected subjects after 1 year of HAART compared to control participants (P < 0.05)

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Summary

Introduction

Cytokines can be classified as pro and anti-inflammatory and are considered important initiators and mediators of inflammation [1]. IFN-γ acts by activating macrophages and is essential for eliminating intracellular pathogens [4] Most of these cytokines have been used as hallmarks of disease progression as well as assessment of patient’s response to antiretroviral treatment [5]. During the course of HIV-1 infection, secretion of T-helper type 1 (Th 1) cytokines such as interleukin (IL-2) and interferon gamma (IFN-γ) are generally decreased, whereas production of T helper 2 (Th 2) cytokines IL-4, IL-10, proinflammatory cytokines (IL-1, IL-6, IL-8) and tumour necrosis factor TNF-α are increased [6] Such abnormal cytokine production contributes to the pathogenesis of the disease by impairing cell-mediated immunity [7]. This study was designed to determine the effects of HIV and Highly Active Antiretroviral Therapy (HAART) on the levels of pro-and anti-inflammatory cytokines in HIV infected subjects

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