DYSREGULATION OF INTERLEUKIN-8, INTERLEUKIN-10, AND INTERLEUKIN-12 RELEASE BY ALVEOLAR MACROPHAGES FROM HIV TYPE-1-INFECTED SUBJECTS

We examined the in vitro release of interleukin 8 (IL-8), interleukin 10 (IL-10), and interleukin 12 (IL-12) by alveolar macrophages from no rmal volunteers and HIV-1-infected subjects. Normal volunteers had ver y low levels of IL-8 and IL-10 and undetectable IL-12 in the cell-free bronchoalveolar lavage fluid (BALF). Asymptomatic HIV-1-infected subj ects had elevated levels of IL-8 and IL-10 in their BALF, and HIV-1-in fected subjects with nonspecific interstitial pneumonitis (NIP) or inf ected with Pneumocystis carinii had the highest BALF levels of IL-10 a nd IL-8. It was found that alveolar macrophages from asymptomatic HIV- 1 subjects and from NIP subjects spontaneously released elevated IL-8, IL-10, and IL-12. However, AIDS subjects infected with P. carinii had cells that released elevated levels of IL-10 and IL-8, but low levels of IL-12. When alveolar macrophages were stimulated with Staphylococc us aureus Cowan (SAG), cells from normal volunteers responded with a c onsiderably increased release of IL-8, IL-10, and IL-12; cells from HI V-1-infected subjects without P. carinii infection responded with a mo derate increase in release of all three monokines, SAC stimulation did not enhance the release of monokines by cells from AIDS subjects with P. carinii infection, and IL-12 levels remained low. There was no str ict relationship between spontaneous cytokine release and p24 HIV-1 an tigen expression by alveolar macrophages. Finally, we showed that neut ralizing IL-10 production by alveolar macrophages from AIDS subjects s ubstantially increased IL-12 releasability. These data suggest that HI V-1 infections determine a dysregulation of IL-8 and of two key mediat ors in determining an immune response, namely IL-10 and IL-12.