Rapid and Slow Progressors Show Increased IL-6 and IL-10 Levels in the Pre-AIDS Stage of HIV Infection.

Rúbia M De Medeiros,Jose Artur B Chies,Sabrina E M Almeida,Marineide G De Mello,Tiago Gräf,Dennis M Junqueira,Jacqueline M Valverde-Villegas,Priscila Vianna,Juliana D Lindenau,Anil Kumar

doi:10.1371/journal.pone.0156163

Abstract

Cytokines are intrinsically related to disease progression in HIV infection. We evaluated the plasma levels of Th1/Th2/Th17 cytokines in extreme progressors, including slow (SPs) and rapid (RPs) progressors, who were thus classified based on clinical and laboratory follow-up covering a period of time before the initiation of HAART, ranging from 93–136.5 months for SPs and 7.5–16.5 months for RPs. Analyses were also performed based on the different stages of HIV infection (chronic, pre-HAART individuals—subjects sampled before initiating HAART but who initiated therapy from 12 to 24 months—and those receiving HAART). The plasma cytokine levels of 16 HIV-infected rapid progressors and 25 slow progressors were measured using a Human Th1/Th2/Th17 CBA kit. The IL-6 and IL-10 plasma levels differed significantly between the stages of HIV infection. The IL-6 levels were higher in slow progressors pre-HAART than in chronically infected SPs and HIV-seronegative individuals. The IL-10 levels were higher in slow progressors pre-HAART than in slow progressors receiving HAART and HIV-seronegative controls, and in rapid progressors, the IL-10 levels were higher in pre-HAART subjects than in HIV-seronegative controls. The results reflect the changes in the cytokine profile occurring during different clinical stages in HIV+ subjects. Our results suggest an association between increased IL-6 and IL-10 levels and pre-HAART stages independent of the slow or rapid progression status of the subjects. Thus, increased IL-6 and IL-10 levels could indicate a global inflammatory status and could be used as markers of the disease course in HIV-infected individuals.

Highlights

HIV infection progression is commonly defined based on the stability of CD4+ T-cell counts, viral load and the duration of symptom-free HIV infection [1,2]
Global comparisons revealed that the IL-6 and IL-10 levels differed between the stages of HIV infection (p = 0.03 and p = 0.02, respectively)
Among the slow progressors’ (SPs), the IL-6 levels were higher in the pre-highly active antiretroviral therapy (HAART) stage (2.59 pg/mL) than in the chronic stage (2.15 pg/ mL, p = 0.001), and the IL-10 levels were higher in those in the pre-HAART stage (2.18 pg/ mL) than in patients receiving HAART (1.55 pg/mL, p = 0.04)

Summary

Introduction

HIV infection progression is commonly defined based on the stability of CD4+ T-cell counts, viral load and the duration of symptom-free HIV infection [1,2]. Subjects with stable CD4+ Tcell counts and other clinical and immunological parameters over a period ranging from 7 to 10 years or more are known as ‘slow progressors’ (SPs). These individuals represent between 5% and 15% of the HIV-infected population [3,4]. Plasma cytokine levels have been postulated to change dramatically over the course of HIV infection [6,7,8]. Several studies suggest that cytokine levels are different in distinct stages of HIV infection, little is known about this topic in subjects classified according to rapid or slow disease progression

Methods

Results

Conclusion