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 (dlco),hiv1+ nonsmokers,and hiv1+ smokers with low dlco. results. increased levels of the th17 related cytokine il-23 were found in hiv1- smokers with low dlco 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 dlco. 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. © 2016 igor z. barjaktarevic et al.