Ex vivo modulation of RANTES and sCD30 by proinflammatory stimuli in HIV-seropositive and -negative individuals

RANTES and sCD30 were measured in ex rico culture supernatants of unstimula ted or stimulated PBMC in order to investigate their potential role as mark ers of acute immune activation, Patients in an advanced stage of HIV infect ion (AIDS A) were compared to AIDS patients who were evaluated for pneumoni a at the time of blood withdrawal (AIDS B); HIV+ individuals with nonprogre ssive infection (LTNP) and healthy donors (N) served as controls. Constitut ive levels of RANTES were significantly elevated in AIDS B patients (P 0.00 01), whereas spontaneous release of sCD30 was strongly correlated with the presence of both pneumonia (P 0.002) and HIV infection (P 0.004). LPS was a strong inducer of RANTES in all four categories; however, in AIDS B patien ts a negative and positive correlation between constitutive and induced lev els was observed with LPS (P 0.0004) and IFN-gamma (P 0.006), respectively. We clearly showed that IFN-gamma reached a fourfold superinduction of sCD3 0 release in both HIV-positive and -negative individuals, whereas IL-6-driv en production of both sCD30 and RANTES occurred only in healthy donors. Ex vivo RANTES levels may also be monitored as an index of acute immune activa tion under conditions of chronic activation of the immune system, whereas s CD30 release may be equally indicative of both acute and chronic processes of T cell activation. Proinflammatory stimuli differentially affected RANTE S and sCD30 secretion in ex rico PBMC cultures, suggesting complex pathways in the in rico regulation of these two molecules. (C) 2000 Academic Press.