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 mechanism by which local and systemic inflammatory processes are regulated during lung transplantation, we measured this cytokine concentration in the serum and bronchoalveolar lavage fluid (BALF) collected in 27 lung recipients. IL-6 bioactivity was analyzed using a B cell hybridoma proliferation assay (B9 cell line). Three groups of clinical situations were analyzed: control lung recipients, rejections, and CMV pneumonia. Serum IL-6 concentrations (mean +/- SEM) were 24.2 +/- 3.3 U/ml in the 26 control samples. In 20 allograft rejection episodes, the serum IL-6 concentration was higher than in control samples but the difference was not significant (59.3 +/- 20.5 U/ml, P>0.05). IL-6 serum levels 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 rejection 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 results 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 BALF was produced in situ during CMV pneumonia as shown by in situ hybridization experiments that revealed a significant number of IL-6 gene-expressing 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 produced within lung transplants during CMV pneumonia, and to a lesser extent during allograft rejection.