EFFECTS OF RADIOLABELED MURINE ANTIBODY INFUSION ON TNF-ALPHA, IL-1-BETA, AND SOLUBLE IL-2 RECEPTOR IN CANCER-PATIENTS

This study evaluates the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and soluble IL-2 receptor (sIL-2R) in cancer patients infused with radiolabelled murine monoclo nal antibodies (MAbs) for the purposes of imaging and dosimetry. Blood samples were collected from 13 patients (10 with colon cancer and 3 w ith lung cancer) before and at 4 and 7 days after infusion of either c onventional intact In-111-MAb or a bifunctional antibody delivery syst em. For all subjects, except one, this was the first exposure to murin e MAb. Before infusion, higher levels of TNF-alpha, IL-1 beta, and sIL -2R than the average expected in the plasma of healthy individuals wer e found. A significant decrease was noted in TNF-alpha when preinfusio n concentrations were compared to 4 day (P<0.01) or to 7 day (P<0.05) postinfusion values. A 50% or greater decrease in IL-1 beta was also o bserved in most individuals with time after infusion. In contrast, sIL -2R concentrations remained relatively stable during the 1 week follow -up period. However, strikingly different patterns in the IL-1 beta an d sIL-2R levels were noted in the subject who had received two previou s murine antibody infusions. Our data show that the administration of radiolabelled murine antibodies, either conventional or bifunctional, can significantly alter plasma levels of TNF-alpha and IL-1 beta. Thes e cytokines are important in immunoregulation and, perhaps also, in mo dulation of neoplastic growth. (C) 1994 Wiley-Liss, Inc.