Interleukin-4 and Interferon-Gamma Production during HIV-1 Infection and Changes Induced by Antiretroviral Therapy

Abstract

Several lines of evidence indicate that a switch of the cytokine pattern from a predominant type 1 (antiviral and cell mediated response) to type 2 (polyclonal humoral immune response) occurs during the course of Human Immunodeficiency Virus-1 (HIV-1) infection, and represents a key event in the progression of immunodeficiency and dysregulated immune activation. We proposed to further investigate this immunological aspect of HIV-1 disease, in naive and in patients treated with Highly Active Antiretroviral Therapy (HAART). The prototypic cytokines chosen were Interleukin (IL)-4 and Interferon-gamma (IFN-γ), whose in vitro production was determined in mononuclear cell cultures stimulated with different T lymphocyte mitogenic agents (anti-CD3, Phytohaemoagglutin-P -PHA-, E. coli B04/035 Lipopolysaccharide -LPS-). We classified all the patients on the basis of the number of CD4+ lymphocytes and we found a progressive, even if not significant decrease in the baseline production of IFN-γ with the progression of the immunodeficiency. The mean value of baseline IFN-γ in the group of patients with CD4+>500 cells/μL was 7.79+3.1 pg/mL while in the group with CD4+<200 cells/μL it was 4.66±2.22. We didn't find significant differences in the baseline production of IL-4 in these groups and in IFN-γ and IL-4 production in LPS-stimulated cultures. We also re-assessed 12 patients after one year's follow-up. They presented a significant increase in IFN-γ production compared to the first assessment in the LPS-stimulated cultures (baseline IFN-γ 2.87+1.17 pg/mL, after 12 months 19.15±5.19 pg/mL; p= 0.03). In the 12 patients in follow-up IL-4 production showed a decreased in PHA-stimulated cultures with mean values of 16.65±14.32 pg/mL at baseline and 6.54±6.54 pg/mL after follow-up. These results highlight the immunorestoring effects of HAART. IL-4 production was lower in the treated subjects compared to the naive ones in PHA-stimulated cultures (mean values: IL-4=13.42 ±11.08 pg/mL in the naive patients and 9.75 ±65 pg/mL in the treated patients). The IFN-γ values in anti-CD3 stimulated cultures were also higher in the treated patients, but this increase was not significant.