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

<div><p>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.</p></div

Clinical baselines and demographic characteristics of the 41 HIV-infected subjects enrolled in this study as rapid or slow disease progressors.

<p>Clinical baselines and demographic characteristics of the 41 HIV-infected subjects enrolled in this study as rapid or slow disease progressors.</p

Plasma cytokine levels in rapid and slow progressors subgrouped according to clinical stage.

<p>Plasma levels of the cytokines IL-2, IFN-γ, IL-4, IL-6, TNF-α, IL-17A and IL-10 in rapid (green) and slow (blue) progressors grouped by different stages of HIV infection and in HIV-seronegative controls (red). A Kruskal Wallis test showed significant differences between the IL-6 levels for chronically infected<i>vs</i> pre-HAART SPs (p = 0.001) and pre-HAART SPs<i>vs</i> HIV-seronegative individuals (p = 0.01). In addition, significant differences were observed in the IL-10 levels between pre-HAART SPs<i>vs</i> SPs receiving HAART (p = 0.04); pre-HAART SPs<i>vs</i> HIV-seronegative individuals (p = 0.02); and pre-HAART RPs<i>vs</i> HIV-seronegative individuals (p = 0.01). After FDR, significant differences were maintained for the IL-6 levels in chronically infected<i>vs</i> pre-HAART SPs (p = 0.03) and the IL-10 levels in pre-HAART RPs<i>vs</i> HIV-seronegative individuals (p = 0.01).</p

Flowchart of the sampling procedure.

<p>Flowchart of the sampling procedure.</p

IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17A plasma levels in HIV-seronegative control and HIV-seropositive individuals grouped by different clinical stages of HIV infection.

<p>IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17A plasma levels in HIV-seronegative control and HIV-seropositive individuals grouped by different clinical stages of HIV infection.</p

IL-6 and IL-10 plasma levels in slow progressors in a pre-HAART stage.

<p>A significant Spearman correlation, rho = 0.750, was observed between theIL-6 and IL-10 plasma levels in pre-HAART SPs (p = 0.02).</p