Soluble TNF receptors (TNF-sR55 and TNF-sR75) in lung allograft recipients displaying cytomegalovirus pneumonitis.
Two distinct types of tumor necrosis factor receptors (TNF-R) have been identified (TNF-R55 and TNF-R75). Both TNF-R also exist in soluble forms (TNF-sR), resulting from the release of the extracellular domains (TNF-sR55 and TNF-sR75). 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-sR55 and TNF-sR75. 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-sR55 and TNF-sR75 concentrations were measured by enzyme-linked immunologic binding assay. Serum TNF-sR55 and TNF-sR75 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, TNF-sR55, and TNF-sR75 serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Humbert
M
M
Laboratoire d'Immunopathologie et d'Immunologie Virale, INSERM U131, Clamart, France.
Roux-Lombard
P
P
Cerrina
J
J
Magnan
A
A
Simonneau
G
G
Dartevelle
P
P
Galanaud
P
P
Dayer
J M
JM
Emilie
D
D
D000328:Adult; D015703:Antigens, CD; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006084:Graft Rejection / Q000097:blood* / Q000276:immunology / Q000473:pathology; D006801:Humans; D016014:Linear Models; D017563:Lung Diseases, Interstitial / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D016040:Lung Transplantation / Q000009:adverse effects*; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D015375:Receptors, Interleukin-2 / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis* / Q000145:classification; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015703:Antigens, CD; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D001708:Biopterins; D019798:Neopterin; D003404:Creatinine; D015774:Ganciclovir