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, IFNγ, IL2) and type 2 (IL4, IL10) cytokine profiles may be associated with virological parameters of progression of the disease in HIV‐1‐infected patients. The production of cytokines was studied in LPS + PHA‐activated whole‐blood culture in HIV‐1‐infected individuals at different stages of the disease. The association was investigated between IL12p40 and IL12p70 profiles and other cytokines (IFNγ, IL4, IL10), as well as the isolation of cytopathogenic HIV‐1 strains. The phenotype of HIV strains was studied by a micromethod based on P4 cell line, allowing detection of cytopathic effects of HIV‐1 isolates (syncytium‐induction and cell‐killing without syncytium induction). The individual variations in IL12p40 and IL12p70 production were limited in the healthy controls. Low values were observed in HIV‐1‐infected patients. The production of IL12 (p40 and p70) and the IL12p70/IL4 ratio and the IFNγ/IL4 ratio were significantly lower in patients with cytopathic isolates compared with patients with noncytopathic isolates, and a correlation was obtained between the values of IL12 (IL12p40 and IL12p70) and those of IFNγ/IL4 ratio. There 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, IFNγ) in the presence of a relatively preserved production of type 2 cytokines (IL4, IL10) in HIV‐1‐infected patients. In conclusion, the defect of production of IL12 by whole blood is associated with virological correlates of progression of HIV‐1 disease. J. Med. Virol. 55:209–214, 1998. © 1998 Wiley‐Liss, Inc.