Effects of radiolabelled 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 monoclonal antibodies (MAbs) for the purpose of imaging and dosimetry. Blood samples were collected from 13 patients (10 with colon cancer and 3 with lung cancer) before and at 4 and 7 days after infusion of either conventional intact 111In-MAb or a bifunctional antibody delivery system. For all subjects, except one, this was the first exposure to murine MAb. Before infusion, higher levels of TNF-alpha, IL-1 beta, and sIL-2R than the average expected in the plasma of healthy individuals were found. A significant decrease was noted in TNF-alpha when preinfusion 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 observed 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 and sIL-2R levels were noted in the subject who had received two previous 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. These cytokines are important in immunoregulation and, perhaps also, in modulation of neoplastic growth.
Gridley
D S
DS
Department of Microbiology, Loma Linda University/Independent Order of Foresters Cancer Research Laboratory, Loma Linda University School of Medicine, California 92350.
Hammond
S N
SN
Slater
J M
JM
D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging; D016719:Radioimmunodetection; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D007375:Interleukin-1; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha