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

الملخص EN

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 ( D L C O ), HIV1+ nonsmokers, and HIV1+ smokers with low D L C O .

Results.

Increased levels of the Th17 related cytokine IL-23 were found in HIV1− smokers with low D L C O 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 D L C O .

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.