Upregulation of IL-17 in acute rejection after lung transplantation

Abstract

Acute rejection (AR) episodes of the transplanted lung are a significant cause of morbidity and increase the risk of developing chronic rejection and obliterative bronchiolitis (OB). Histopathologically, AR is characterized by perivascular mononuclear infiltration and lymphocytic bronchiolitis. In addition, infiltration of neutrophils has been observed, which could possibly feature as an early indicator of the development of OB. In the current study, we have investigated the composition of inflammatory cells in BAL as well as the expression of important cytokines during episodes of AR, confirmed by TBB (n 12, 6 SLTX and 6 SSLTX, 5 grade 1 AR, 6 grade 2 AR and 1 grade 3 AR). As controls (CTRL), BAL samples from patients without any evidence of rejection on TBB or infection were analyzed (n 8, 3 SLTX and 5 SLTX). The cell suspension from the BAL samples was cytocentrifuged onto microscopic slides and differential counts were performed. Expression of cytokines was analyzed by means of real-time PCR. AR was associated with a significant increase of BAL lymphocytes (17.5 4.1% in AR vs. 4.4 4.0% in CTRL, p 0.05) and a rise in the number of BAL neutrophils (21.1 5.7% in AR vs. 8.5 3.6% in CTRL). There was also a significantly increased expression of IL-17 in BAL samples of patients with an AR (0.26 0.1 pg/ml in AR vs. 0.09 0.02 pg/ml in CTRL, p 0.05), while IL-8, IL-6 and TNF-alfa mRNA levels remained unchanged. We concluded that the lymphocyte derived cytokine IL-17 is upregulated in BAL samples from lung transplant patients during AR episodes. As IL-17 is capable of inducing IL-8 release and thus promoting neutrophilic infiltration, IL-17 may also be important in the progression from active to chronic rejection after lung transplantation.