Assessment of type 1 and type 2 cytokines in HIV type 1-infected individuals: Impact of highly active antiretroviral therapy

Although the effect of highly active antiretroviral therapy (HAART) on HIV- 1 replication has been established, the mechanisms involved in restoration of immune responses and reconstitution remain unknown. This study provides evidence of changes in expression of type 1 and type 2 cytokine-specific mR NA occurring during HIV-1 infection, before and after initiation of HAART, Unstimulated PBMCs from nine HIV-1-infected individuals obtained at differe nt time intervals before and after the initiation of HAART were assessed fo r specific IFN-gamma, IL-2, IL-4, and IL-10 mRNA expression, using RT-PCR, Correlation with CD4(+) T cell counts and viral load was also carried out. Before initiation of HAART, in all patients, little expression of specific IFN-gamma and IL-2 (type 1 cytokine) mRNA was noted. In contrast, expressio n of specific IL-4 and/or IL-10 (type 2) mRNA was readily detectable in the majority of patients. After initiation of HAART there was a continuous inc rease in IFN-gamma and IL-2 mRNA expression, although the latter occurred i n lower amounts. This paralleled a dramatic reduction in viral load and inc rease in CD4(+) T cell counts, Type 2 cytokine-specific mRNA expression fel l to undetectable levels and in some cases reappeared later in the course o f HAART, Predominant expression of type 2 cytokine mRNA, before initiation of HAART, concurs with previous findings of a dominant antiproliferative, t ype 2 cytokine profile during HIV-1 infection. Reversion of the cytokine pr ofile, after HAART, to a strong type 1 profile suggests that in addition to suppressing virus replication directly the immune system may be given a ch ance to recover.