Role of cytokine profile in the differential diagnosis between acute lung rejection and pulmonary infections after lung transplantation

Acute lung rejection (ALR) is a relatively frequent complication during the first year after lung transplantation (LT). It is characterized by perivascular/bronchial mononuclear inflammation mediated by several cytokines. The aim of our study was to monitor a panel of cytokines extracted from the bronchoalveolar lavage (BAL) during the first year after LT and correlate them with clinical ALR. Twenty double lung transplant recipients were prospectively assessed. Fifteen (75%) were affected by cystic fibrosis (CF). BAL was collected at seven different steps (pretransplant, immediately post-transplant, after 1 week, 1, 3, 6 months and 1 year). A panel of six cytokines was analysed: tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, macrophage inflammatory protein (MIP)-1 alpha and IL-10. We correlated the cytokine levels with clinical ALR episodes, bacterial and cytomegalovirus (CMV) infections. One hundred and thirty-eight BAL samples were collected and analysed. In CF patients, the levels of proinflammatory cytokines significantly dropped immediately after the transplant while they increased in all the other patients. Four patients (20%) died between 6 months and 1 year. Nine patients (45%) showed one clinical ALR episode within 6 months; in 6 (30%) patients, a bacterial pneumonia was diagnosed and 5 (25%) developed CMV infection. No differences with the complication rate between CF and non-CF patients were observed. During the infection episodes, all proinflammatory cytokines increased with low levels of IL-10; in case of ALR, levels of IL-1 beta and MIP-1 alpha increased significantly (P = 0.01 and P < 0.0001), IL-10 levels were higher compared with the infection episodes (P = 0.03). No significant changes were observed for TNF-alpha, IL-6 and IL-8. The BAL cytokine profile (IL-1 beta, MIP-1 alpha and IL-10) seems useful to differentiate ALR and infections.