IMBALANCE IN CYTOKINE PRODUCTION BY WHOLE-BLOOD RELATED TO PRESENCE OF CYTOPATHOGENIC HIV-1 STRAINS IN HIV-1-INFECTED PATIENTS

The possible association between the emergence of cytopathogenic HIV-1 variants and disturbance of the cytokine production in the course of HIV-1 infection was studied in 18 infected patients. The cytopathogeni city of the isolates was studied in a microassay based on the use of H IV-1-infectible Hela-CD4 cells carrying the bacterial LacZ gene under the control of the HIV-LTR (P4 cells). In addition, the production of cytokines by heparinized whole blood (HWB) obtained the same day from HIV-1(+) patients was measured. TNF-alpha was determined in a one-step procedure combining HWB culture in the presence of LPS+PHA for 24 h a nd detection of cytokines in the same wells. In separate experiments H WB was cultured in the presence of LPS+PHA for 48 h, then the supernat ants were collected and stored until assayed by ELISA for IFN-gamma an d IL-4. Higher TNF-alpha levels were found in activated HWB of patient s with cytopathic strains (n = 9) than in patients with non-cytopathic strains (n = 9, p = 0.02) as assed with P4 cells. A defective product ion of type 1 cytokine (IFN-gamma) and no increased secretion of type 2 cytokines (IL-4) was observed in patients,vith cytopathic strains. I FN-gamma/IL-4 ratios were significantly lower in patients with cytopat hic strains (n = 9) than in other patients (n = 9, p = 0.009). The res ults show that the disarray of cytokine production, as assessed with w hole blood culture, is associated with the cytopathogenicity of HIV-1 isolates in HIV-1-infected individuals.