CLINICAL AND IMMUNOLOGICAL EFFECTS OF HUMAN RECOMBINANT INTERLEUKIN-2GIVEN BY REPETITIVE WEEKLY INFUSION TO NORMAL DOGS

Four normal adult dogs received two consecutive weekly cycles of human recombinant interleukin-2 (IL-2) by continuous infusion for 4 days/we ek. The dose of IL-2 given to each dog was 3 x 10(6) units m-(2) day-( 1). Toxicities consisted of mild vomiting, diarrhea, and lethargy to v arying degrees in all the dogs. These side-effects were reversed when the treatment was discontinued. Fever, tachypnea, and weight gain were not seen. A marked lymphocytosis and eosinophilia developed in all do gs after completion of each course of IL-2 (resulting in a more than s evenfold increase in each cell type) and persisted for more than 1 mon th in some. Fresh peripheral blood lymphocytes (PBL) obtained during t his lymphocytosis mediated enhanced in vitro lysis of a natural-killer -cell-sensitive canine tumor cell line (CTAC). The in vitro proliferat ive responses of these same PBL to IL-2 could be detected earlier, pro gressed faster, and involved more cells than PBL tested prior to IL-2 infusion. Thus, a relatively well-tolerated regime of IL-2 in dogs can induce dramatic increases in Iymphocyte numbers and activation, which is associated with augmentation of their in vitro antitumor reactivit y. The clinical effectiveness of this immunotherapeutic approach remai ns to be tested in tumor-bearing dogs where it could serve as a releva nt large-animal model for immunotherapy of cancer with IL-2.