Dysregulation of Interleukin 8,Interleukin 10,and Interleukin 12 Release by Alveolar Macrophages from HIV Type 1-Infected Subjects

Abstract

We examined the in vitro release of interleukin 8 (IL-8), interleukin 10 (IL-10), and interleukin 12 (IL-12) by alveolar macrophages from normal volunteers and HIV-1-infected subjects. Normal volunteers had very low levels of IL-8 and IL-10 and undetectable IL-12 in the cell-free bronchoalveolar lavage fluid (BALF). Asymptomatic HIV-1-infected subjects had elevated levels of IL-8 and IL-10 in their BALF, and HIV-1-infected subjects with nonspecific interstitial pneumonitis (NIP) or infected with Pneumocystis carinii had the highest BALF levels of IL-10 and 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 Staphylococcus aureus Cowan (SAC), cells from normal volunteers responded with a considerably increased release of IL-8, IL-10, and IL-12; cells from HIV-1-infected subjects without P. carinii infection responded with a moderate 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 strict relationship between spontaneous cytokine release and p24 HIV-1 antigen expression by alveolar macrophages. Finally, we showed that neutralizing IL-10 production by alveolar macrophages from AIDS subjects substantially increased IL-12 releasability. These data suggest that HIV-1 infections determine a dysregulation of IL-8 and of two key mediators in determining an immune response, namely IL-10 and IL-12.