A DECREASED PRODUCTION OF IL12 IN-VITRO IS ASSOCIATED WITH ISOLATION OF CYTOPATHIC HIV-1 STRAINS IN HIV-1-INFECTED PATIENTS

The changes in type 1 (IL12, IFN gamma, IL2) and type 2 (IL4, IL10) cy tokine profiles may be associated with virological parameters of progr ession of the disease in HIV-1-infected patients. The production of cy tokines was studied in LPS + PHA-activated whole-blood culture in HIV- l-infected individuals at different stages of the disease. The associa tion was investigated between IL12p40 and IL12p70 profiles and other c ytokines (IFN gamma, IL4, IL10), as well as the isolation of cytopatho genic HIV-1 strains. The phenotype of HIV strains was studied by a mic romethod based on P4 cell line, allowing detection of cytopathic effec ts of HIV-1 isolates (syncytium-induction and cell-killing without syn cytium induction). The individual variations in IL12p40 and IL12p70 pr oduction were limited in the healthy controls. Low values were observe d in HIV-1-infected patients. The production of IL12 (p40 and p70) and the IL12p70/IL4 ratio and the IFN gamma/IL4 ratio were significantly lower in patients with cytopathic isolates compared with patients with noncytopathic isolates, and a correlation was obtained between the va lues of IL12 (IL12p40 and IL12p70) and those of IFN gamma/IL4 ratio. T here was no increase in the secretion of IL4 and IL10 in patients with cytopathic strains compared with other patients. The results indicate a decreased production of type 1 cytokines (IL12, lFN gamma) in the p resence of a relatively preserved production of type 2 cytokines (IL4, IL10) in HIV-1-infected patients. In conclusion, the defect of produc tion of IL12 by whole blood is associated with virological correlates of progression of HIV-1 disease. (C) 1998 Wiley-Liss, Inc.