Infusion of tumor necrosis factor (TNF) causes an increase in circulating TNF-binding protein in humans.
Serum samples from cancer patients receiving intravenous infusions of recombinant tumor necrosis factor (rTNF) and recombinant interferon-gamma (rIFN-gamma) were analyzed for TNF and the TNF-binding protein (TNF-BP). TNF-BP is a soluble fragment of the transmembrane TNF receptor with antagonistic effects to TNF and is released by proteolytic cleavage of the receptor. During a 60-min infusion of rTNF, peak serum levels of rTNF were observed after 30 to 60 min and a transient increase of circulating TNF-BP was observed with peak levels between 30 and 120 min. Injection of IFN-gamma alone did not affect the levels of TNF and TNF-BP. Thus administration of rTNF leads to release into the circulation of TNF-BP, which may modulate both systemic and local effects of TNF and influence its therapeutic efficacy.
Lantz
M
M
Division of Hematology, Department of Medicine, Lund, Sweden.
Malik
S
S
Slevin
M L
ML
Olsson
I
I
D002352:Carrier Proteins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007262:Infusions, Intravenous; D007371:Interferon-gamma / Q000627:therapeutic use; D007700:Kinetics; D009369:Neoplasms / Q000628:therapy*; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use*
D002352:Carrier Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1; D007371:Interferon-gamma