The Role of Interleukin-23 in the Early Development of Emphysema in HIV1(+) Smokers

Rationale. Matrix metalloproteinase-9 (MMP-9) expression is upregulated in alveolar macrophages (AM) of HIV1(+) smokers who develop emphysema. Knowing that lung epithelial lining fluid (ELF) of HIV1(+) smokers contains increased levels of inflammatory cytokines compared to HIV1(−) smokers, we hypothesized that upregulation of lung cytokines in HIV1(+) smokers may be functionally related to increased MMP-9 expression. Methods. Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1(−) healthy nonsmokers, HIV1(−) healthy smokers, HIV1(−) smokers with low diffusing capacity (DL(CO)), HIV1(+) nonsmokers, and HIV1(+) smokers with low DL(CO). Results. Increased levels of the Th17 related cytokine IL-23 were found in HIV1(−) smokers with low DL(CO) and HIV1(+) smokers and nonsmokers. Relative IL-23 gene expression was increased in AM of HIV1(+) individuals, with greater expression in AM of HIV1(+) smokers with low DL(CO). Infection with HIV1 in vitro induced IL-23 expression in normal AM. IL-23 stimulation of AM/lymphocyte cocultures in vitro induced upregulation of MMP-9. Lung T lymphocytes express receptor IL-23R and interact with AM in order to upregulate MMP-9. Conclusion. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1(+) smokers and suggests that Th17 related inflammation may play a role.