IN-SITU PRODUCTION OF INTERLEUKIN-6 WITHIN HUMAN LUNG ALLOGRAFTS DISPLAYING REJECTION OR CYTOMEGALOVIRUS PNEUMONIA

Interleukin-6 (IL-6) is a pleiotropic cytokine that is a regulator of inflammation and immunity. As production of IL-6 may be an important m echanism by which local and systemic inflammatory processes are regula ted during lung transplantation, we measured this cytokine concentrati on in the serum and bronchoalveolar lavage fluid (BALF) collected in 2 7 lung recipients. IL-6 bioactivity was analyzed using a B cell hybrid oma proliferation assay (B9 cell line). Three groups of clinical situa tions were analyzed: control lung recipients, rejections, and CMV pneu monia. Serum IL-6 concentrations (mean +/- SEM) were 24.2 +/- 3.3 U/ml in the 26 control samples. In 20 allograft rejection episodes, the se rum IL-6 concentration was higher than in control samples but the diff erence was not significant (59.3 +/- 20.5 U/ml, P>0.05). IL-6 serum le vels were significantly increased during the 14 CMV pneumonias (61.2 /- 11.5 U/ml, P<0.01). In BALF, IL-6 levels were increased during CMV pneumonia (52.4 +/- 21.9 U/ml BALF), and to a lesser extent during rej ection events (14.1 +/- 3.7 U/ml BALF), as compared with controls (5.6 +/- 1.6 U/ml BALF, P<0.005, and P<0.05, respectively). Similar result s were observed when IL-6/albumin and IL-6/urea ratios were determined so as to compensate for possible dilution effects in BALF. IL-6 in BA LF was produced in situ during CMV pneumonia as shown by in situ hybri dization experiments that revealed a significant number of IL-6 gene-e xpressing alveolar cells in this condition. IL-6 concentrations in the serum and in the BALF were compared. There was no correlation between serum and BALF IL-6 concentrations, showing that serum IL-6 levels do not accurately reflect intrapulmonary IL-6 production. Thus IL-6 is p roduced within lung transplants during CMV pneumonia, and to a lesser extent during allograft rejection.