Alterations in circulating measures of Th2 immune responses pre-lung transplant associates with reduced primary graft dysfunction

Abstract

Primary graft dysfunction (PGD) is a complication of lung transplantation that continues to cause significant morbidity. The Th2 immune response has been shown to counteract tissue-damaging inflammation. We hypothesized that Th2 cytokines/chemokines in blood would be associated with protection from PGD. Utilizing pretransplant sera from the multicenter clinical trials in organ transplantation study, we evaluated Th2 cytokines/chemokines in 211 patients. Increased concentrations of Th2 cytokines were associated with freedom from PGD, namely IL-4 (odds ratio [OR] 0.66 [95% confidence interval {CI} 0.45-0.99], p = 0.043), IL-9 (OR 0.68 [95% CI 0.49-0.94], p = 0.019), IL-13 (OR 0.73 [95% CI 0.55-0.96], p = 0.023), and IL-6 (OR 0.74 [95% CI 0.56-0.98], p = 0.036). Multivariable regression performed for each cytokine, including clinically relevant covariables, confirmed these associations and additionally demonstrated association with IL-5 (OR 0.57 [95% CI 0.36-0.89], p = 0.014) and IL-10 (OR 0.55 [95% CI 0.32-0.96], p = 0.035). Higher levels of Th2 immune response before lung transplant appear to have a protective effect against PGD, which parallels the Th2 role in resolving inflammation and tissue injury. Pretransplant cytokine assessments could be utilized for recipient risk stratification.

Keywords: Th2; chemokines; cytokines; lung transplantation; primary graft dysfunction.