Obesity Leads to Increased IL-18, Treg Impairment and Increased Risk of PGD

Purpose Lung transplantation (Tx) is a life-saving treatment for terminal lung diseases but long-term outcomes are poor, beginning with possible development of primary graft disease (PGD) in the first few days post-Tx. PGD mainly involves hyperactivation of innate immunity, but as CD4+FOXP3+ T-regulatory (Treg) cells can curtail various types of inflammation, we wondered whether patients who develop PGD might have dysfunctional Treg cells. Methods We studied pre-Tx blood samples from 78 patients listed for lung Tx (40% COPD, 20% IPF, 10% non-IPF interstitial lung disease, 10% sarcoidosis, 20% others), 50 of whom received a lung Tx, and 18 of whom post-Tx developed grade 3 PGD. Results The patients who went on to become PGD+, had a 1.5-fold pre-Tx decrease in their Treg function (p Conclusion Increases in circulating levels of IL-18 in ob/ow patients pre-Tx may serve as an important sign of of the need to check Treg function, since this combination may lead to increased innate immune activation and become a major risk for PGD, with consequent negative effects on short- and long-term outcomes post-Tx.