Involvement of interleukin-17 during lymphocytic bronchiolitis in lung transplant patients

Abstract

Interleukin-17 (IL-17) is involved in autoimmune and chronic pulmonary diseases and linked with neutrophilic inflammation. Azithromycin reduces and prevents broncholaveolar lavage (BAL) neutrophilia after lung transplantation (LTx). In this investigation we assessed the involvement of IL-17 in different post-transplant complications in human LTx biopsies. Immunohistochemical staining against IL-17A was performed on biopsies of LTx patients with either chronic rejection, acute A-grade rejection (A > 2B0), lymphocytic bronchiolitis (LB), infection, and stable patients. Biopsies of 7 patients with LB were stained before and after azithromycin treatment. IL-17+ cells were quantified as number per square millimeter of lamina propria. Double staining with CD4/CD8 was performed to determine the origin of IL-17. In the LB group, biopsies showed a significant presence of IL-17+ cells/mm2 of lamina propria compared with the stable, acute A-grade/chronic rejection and infection groups (p < 0.0001). The number of IL-17+ cells on biopsy correlated with percent BAL (%BAL) neutrophilia (r = 0.34, p = 0.0056). Azithromycin reduced both %BAL neutrophilia and IL-17+ cells (both p = 0.016) in the LB group. CD8+ cells were the major source of IL-17. IL-17+ / CD8+ cells are present in LB after LTx but not in acute A-grade/chronic rejection nor during infection. Moreover, azithromycin significantly decreased the number of IL-17+ cells in the airway wall, which may further explain its effect on BAL neutrophilia.