Effects of recombinant tumour necrosis factor (rTNF-alpha) in cancer. Observations on the acute phase protein reaction and immunoglobulin synthesis after high dose recombinant TNF-alpha administration in isolated limb perfusions in cancer patients.
To obtain insight in the effect of TNF on the synthesis of acute phase proteins like CRP, alpha 1-antitrypsine, alpha 1-acidglycoprotein, C3 and C4 and the immunoglobulins (IgG-M-A), nine cancer patients who were treated with an isolated limb perfusion (ILP) with high dose recombinant TNF-alpha (rTNF-alpha) were investigated during a 7-day period after the end of the perfusion. Resorption of rTNF-alpha from out of these limbs into the circulation after the ILP induced within 30 min to 6 h in all patients elevated serum levels of IL-6. At the same time C-reactive protein became detectable in serum. The highest serum levels were obtained at 48 h after ILP. The serum levels of the other acute phase proteins (alpha 1-acidglycoprotein, alpha 1-antirypsine, C3, C4), rose more slowly and the highest serum levels were found at the third day. All investigated proteins declined after they had reached their peak levels. Levels of alpha 1-acidglycoprotein and alpha 1-anti-trypsin alpha 1-acid declined slower than both complement component. In regard to the immunoglobulin levels a nearly continuous increase in the serum level of specifically IgM was observed. This study clearly shows the interrelationship between TNF-alpha and IL-6 in regard to the synthesis of the different acute phase proteins; and moreover also a striking effect on IgM synthesis.
Swaak
A J
AJ
Department of Rheumatology, Rotterdam Cancer Institute, The Netherlands.
Lienard
D
D
Schraffordt Koops
H
H
Lejeune
F J
FJ
Eggermont
A M
AM
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D010478:Chemotherapy, Cancer, Regional Perfusion; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D000209:Acute-Phase Proteins; D007136:Immunoglobulins; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein