SOLUBLE TNF RECEPTORS (TNF-SR(55) AND TNF-SR(75)) IN LUNG ALLOGRAFT RECIPIENTS DISPLAYING CYTOMEGALOVIRUS PNEUMONITIS

Two distinct types of tu mor necrosis factor receptors (TNF-R) have been identified (TNF-R(55) and TNF-R(75)). Both TNF-R also exist in soluble forms (TNF-sR), resulting from the release of the extracellular domains (TNF-sR(55) and TNFsR(75)), TNF-sR may play an important role in vivo as they can bind to TNF alpha and prevent ligand binding to the cellular TNF-R, thus acting as naturally occurring inhibitors of TNF alpha. Sera from lung allograft recipients with cytomegalovirus (CMV) pneumonitis (12 patients) were assayed for TNF-sR(55) and TNFsR(75). The concentrations were compared with those from either control lung recipients displaying neither rejection nor infection (12 patients), or lung recipients with allograft rejection (12 patients). Serum TNF-sR(55) and TNF-sR(75) concentrations were measured by enzyme-linked immunologic binding assay. Serum TNF-sR(55) and TNF-sR(75) concentrations were significantly higher during CMV pneumonitis (mean +/- SEM: 13.7 +/- 4.7 ng/ml, and 11.7 +/- 2.7 ng/ml, respectively) than during allograft rejection (3.7 +/- 0.3 ng/ml, p < 0.001, and 2.6 +/- 0.6 ng/ml, p < 0.001, respectively). They were also higher than in control subjects (3.6 +/- 0.3 ng/ml, p < 0.001, and 1.9 +/- 0.5 ng/ml, p < 0.001, respectively). Serum TNF alpha concentration was low in case of rejection or in control subjects (< 20 pg/ml). Conversely increased levels of TNF alpha were detected in the serum of six out of the 12 patients with CMV pneumonitis (p < 0.03 versus rejection and control subjects). Ganciclovir treatment of CMV pneumonitis led to a dramatic decrease of TNF alpha, TNFsR(55), and TNF-sR(75) serum levels. This report demonstrates that there are high levels of TNF-sR in the serum of lung recipients displaying CMV pneumonitis, suggesting a possible mechanism for modulation of excessive macrophage activation arising in response to symptomatic CMV infection.