Elevations in IL-10, TNF-alpha, and IFN-gamma from the earliest point of HIV Type 1 infection

Abstract

Perturbations of plasma IL-10, IL-12, IL-13, TNF-alpha, and IFN-gamma were measured longitudinally in HIV-1 seroconverting plasma donors and were compared to subjects with symptomatic primary HIV-1 infection. Control groups included uninfected patients with symptoms and risks for primary HIV-1, healthy controls, and asymptomatic plasma donors with primary HCV. IL-10, TNF-alpha, and IFN-gamma rapidly rose in acute HIV-1 infection, while IL-13 predominated in acute HCV. Subjects with symptomatic primary HIV-1 had higher cytokine levels than asymptomatic subjects, statistically significant for TNF-alpha. Cytokine alterations occurred within 7 days of detectable HIV-1 viremia, emphasizing the need to study the earliest events of infection.

FIG. 1

Cytokine levels were measured sequentially during the ramp-up phase of HIV-1 (top row) and HCV (middle row) and during resolution of acute HIV-1 in symptomatic patients treated with HAART (bottom row). Time is listed as days from first PCR-positive sample for HIV-1 and HCV ramp-up phases and days from onset of fever for HIV-1 resolution. The final HIV-1 ramp-up timepoint roughly correlates with the first timepoint of symptomatic patients in the bottom row. Notably, the scale for cytokine levels was changed for HIV-1-infected subjects in the resolution phase due to higher cytokine levels in this group. Patient symbols are consistent across rows, and not all cytokines were measured on every patient.

FIG. 2

Correlation of cytokine levels with viral load during the ramp-up phase of HIV-1 (top row) and HCV (middle row) and during resolution of acute HIV-1 in symptomatic patients treated with HAART (bottom row). Only data points obtained before the peak of viremia are shown for HIV-1 and HCV in the ramp-up phase. p-values represent the overall association between each cytokine and log of the viral load. Significant p-values are highlighted in bold. Patient symbols are consistent with those shown in Fig. 1.

FIG. 3

Cytokine levels at the first timepoint for symptomatic HIV⁺ subjects were compared to those at the last timepoint for plasma donors. Only TNF-α showed a statistically significant elevation in symptomatic compared to asymptomatic subjects. Levels were also measured in high-risk HIV-1 seronegative and RNA negative subjects with viral syndrome symptoms and in normal, healthy controls. ND = not done.