Exhaled nitric oxide (eNO) correlates with IL-17 in bronchoalveolar lavage fluid (BALF) during acute lung rejection

Abstract

Despite improved immunosuppression, acute lung rejection (AR) still occurs in 50% of the patients during the first year after lung transplantation (Ltx). Since AR is the major risk factor for OB, unraveling its pathophysiology is very important. We recently demonstrated that IL-17 is increased in BALF of patients with acute rejection (AR), compared to those without AR. IL-17 also stimulates smooth muscle cells to release IL-8, the major chemokine involved in OB. NO seems to be involved in the process of AR, at least in human heart and renal transplantation and in experimental animal transplantation. Although eNO is increased during chronic rejection, it remains a matter of discussion whether eNO is also increased during AR of the lung. The present study aimed to measure eNO and to correlate eNO with IL-17 in BALF of LTx patients with AR and to compare these parameters with a nonacute rejection group. 23 Ltx patients were included in the study. Their mean age at transplantation was 45.8 14.2y. They were all clinically stable and underwent bronchoscopy with BAL and TBB, spirometry and eNO measurements before discharge at postoperative day 24 7 (range 12-41 d). Twelve patients proved to have AR (A1-A3), whereas 11 had A0. There were no significant differences in spirometry between the 2 groups. Compared to the non AR patients (group NAR), those with AR (group AR) had a significant increase of IL-17 in their BALF (0.30 0.12 pg/ml versus 0.06 0.02 pg/ml, p 0.05). The eNO value was 7.5 2.3 ppb in the AR versus 4.9 0.6 ppb in the NAR, p 0.05. For all patients together, there was a significant correlation between IL-17 and eNO (p 0.0013); the correlation remained significant in the AR group only (p 0.048). In Conclusion: the eNO value is not significantly increased during AR, however, the correlation between IL-17 and eNO suggests a potential role for NO during acute lung rejection.