Effects of recombinant tumour necrosis factor (rTNF‐α) in cancer. Observations on the acute phase protein reaction and immunoglobulin synthesis after high dose recombinant TNF‐α administration in isolated limb perfusions in cancer patients

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Abstract
To obtain insight in the effect of TNF on the synthesis of acute phase proteins like CRP, αl‐antitrypsine, αl‐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‐α (rTNF‐α) were investigated during a 7–day period after the end of the perfusion. Resorption of rTNF‐α 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 (α l–acidglycoprotein, αl‐antitrypsine, 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 α1‐‐acidglycoprotein and a,‐anti‐trypsin α1‐‐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‐α and IL‐6 in regard to the synthesis of the different acute phase proteins; and moreover also a striking effect on IgM synthesis.