EFFECTS OF RECOMBINANT TUMOR-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 IL6. 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-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 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.