The role of the IL23/IL17 axis in bronchiolitis obliterans syndrome after lung transplantation

Am J Transplant. 2008 Sep;8(9):1911-20. doi: 10.1111/j.1600-6143.2008.02321.x.


Bronchiolitis obliterans syndrome (BOS) is the leading cause of death after lung transplantation. Treatment is challenging, as the precise pathophysiology remains unclear. We hypothesize that T(H)17 lineage plays a key role in the pathophysiology of BOS by linking T-cell activation to neutrophil influx and chronic inflammation. In a cross-sectional study, bronchoalveolar lavage (BAL) samples of 132 lung transplant recipients were analyzed. Patients were divided in four groups: stable or suffering from infection (INF), acute rejection (AR) or BOS. The upstream T(H)17 skewing (TGF-beta/IL1beta/IL6/IL23), T(H)17 counteracting (IL2), T(H)17 effector cytokine (IL17) and the principal neutrophil-attracting chemokine (IL8), were quantified at the mRNA or protein level in combination with the cell profiles. The BOS group (n = 36) showed an increase in IL1beta protein (x1.5), IL6 protein (x3), transforming growth factor-beta (TGF-beta) mRNA (x3), IL17 mRNA (x20), IL23 mRNA (x10), IL8 protein (x2), IL8 mRNA (x3) and a decrease in IL2 protein (x0.8). The infection group (n = 11) demonstrated an increase in IL1beta protein (x5), IL6 protein (x20), TGF-beta mRNA (x10), IL17 mRNA (x300), IL23 mRNA (x200) and IL8 protein (x6). The acute rejection group (n = 43) only revealed an increase in IL6 protein (x6) and IL8 protein (x2) and a decrease in IL2 protein (x0.7). Lymphocytes and neutrophils were increased in all groups compared to the stable (n = 42). Our findings demonstrate the IL23/IL17 axis to be involved in the pathophysiology of BOS potentially triggering the IL8-mediated neutrophilia. IL6, IL1beta and IL23 seem to be skewing cytokines and IL2 a counteracting cytokine for T(H)17 alignment. The involvement of TGF-beta could not be confirmed, either as T(H)17 steering or as counteracting cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bronchiolitis Obliterans / metabolism
  • Bronchiolitis Obliterans / physiopathology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Cross-Sectional Studies
  • Female
  • Humans
  • Interleukin-17 / physiology*
  • Interleukin-23 / physiology*
  • Lung Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Neutrophils / metabolism
  • RNA, Messenger / analysis
  • Syndrome


  • Interleukin-17
  • Interleukin-23
  • RNA, Messenger