BALANCE BETWEEN ALVEOLAR MACROPHAGE IL-6 AND TGF-BETA IN LUNG-TRANSPLANT RECIPIENTS

Acute inflammation in the lung is characterized by a phase of tissue i njury followed by a phase of tissue repair. When the latter is excessi ve, fibrosis occurs. Alveolar macrophages (AM) can produce cytokines i nvolved in both phases of acute lung inflammation, notably interleukin -6 (IL-6), involved in injury, and transforming growth factor-beta (TG F-beta), mediating repair. We hypothesized that AM were activated in b oth phases, and studied IL-6 and TGF-beta production by AM during comp lications of lung transplantation, acute rejection (AR), and cytomegal ovirus pneumonitis (CMVP). In addition, we analyzed these cytokines in bronchiolitis obliterans (BO), a fibrotic complication of lung transp lantation linked to previous AR and CMVP. At the onset of AR and CMVP, IL-6 secretion increased, whereas AM TGF-beta content was increased, but not its secretion. In contrast, with time, IL-6 reached control va lue whereas TGF-beta secretion rose significantly. In BO, IL-6 was not oversecreted, but TGF-beta increased, notably before functional abnor malities occurred. These results show that during acute complications of lung transplantation, AM display an early activation with oversecre tion of IL-6, which is involved in tissue injury, counterbalanced by a late activation in which TGF-P predominates, mediating tissue repair. The results provide new insights into the pathogenesis of BO, which i s linked to acute complications of lung transplantation through this b iphasic AM activation.