PRODUCTION OF TNF-ALPHA AND IL-6 BY ACTIVATED WHOLE-BLOOD FROM HIV-1-INFECTED PATIENTS DETECTED BY A ONE-STAGE PROCEDURE - RELATIONSHIP WITH THE PHENOTYPE OF HIV-1 ISOLATES

Diluted whole blood (WB) culturing may be the most appropriate milieu in which to study cytokine production in vitro. We tested TNF alpha an d IL-6 production using small volumes of WB (25 mu l) from HIV-1 posit ive patients with a one-step procedure that combines WB stimulation wi th LPS, PHA and cytokine measurement. We studied 49 patients without s econdary infection or at distance of secondary infection staged accord ing to the 1993 classification of the CDC and 12 healthy seronegative subjects. Heparinized blood from 5 control subjects had been collected sequentially during a period of 5 months, The individual variations o f TNF alpha and IL-6 production were limited for all these individuals , In 1 out of 20 CDC group A patients, 6 out of 17 CDC group B patient s and 3 out of 12 CDC group C patients, we obtained higher values of T NF alpha than the mean+2 S.D. of the control group, In 3 out of 20 CDC group A patients, 1 out of 17 CDC group B patients without AIDS and 5 out of 12 CDC group C patients, the TNF alpha values were lower than the mean-2 S.D. of the control group, Low IL-6 values were obtained in 1 out of 20 CDC group A patients and 1 out of 17 CDC group B patients and 3 out of 12 CDC group C patients, There was no correlation betwee n TNF alpha production in vitro and plasma level of TNF alpha. We foun d no correlation between the levels of cytokines and monocyte count or between the levels of cytokines and CD4 T-cell count in peripheral bl ood, Our data point out a disarray in TNF alpha and IL-6 production by WB from HIV-1 infected patients, The relationship between the disarra y of cytokine production and cytopathogenicity of HIV-1 isolates in th e P4 cell line was investigated in this study, We found a correlation between the high level of TNF alpha produced by WB and the phenotype o f HIV-1 isolates isolated from patients, The one-stage procedure used in this work is of potential value to investigate the activation statu s of cells for monitoring HIV-1 positive individuals and predicting HI V-1 phenotype.