Systemic treatment with murine recombinant interleukin-1 beta inhibits the growth and progression of malignant glioma in the rat

Abstract

We investigated the effects of daily subcutaneous (SC) injections of 100, 200, or 400 micrograms/kg murine recombinant interleukin-1 beta (rIL-1 beta) or its excipient on normal Fischer 344 rats and ones harboring a malignant RT-2 glioma. The tumor model has a predictable course with animals dying on days 14-17 following an intracerebral inoculation of 10(4) RT-2 glioma cells. Treatments with rIL-1 beta or excipient began on day seven post-tumor inoculation and continued for 7 days. We observed no significant effect on core body temperatures although there was a significant (p less than 0.05) decrease in body weight in all rIL-1 beta treated animals. When tumor-bearing animals became moribund, they received an intraperitoneal injection of bromodeoxyuridine (BUdr) and were sacrificed two hours later. Blood samples were obtained prior to their sacrifice by transcardiac perfusion with a buffered aldehyde solution. Recombinant IL-1 beta affected blood differentials; causing neutrophilia, lymphopenia, and slight thrombocythemia. The BUdr labeling index of glioma cells did not significantly differ between treatment groups, although tumors differed histologically at the time of necropsy. Tumors of rIL-1 beta treated animals had more extensive necrosis and a greater degree of leukocyte infiltration. Survival studies were conducted in which rats were given continuous daily SC injections of rIL-1 beta until day of death. Overall survival between the two groups differed significantly in studies using 100 micrograms/kg/d (p less than 0.05); rIL-1 beta treated rats had a mean survival time of 22 (+/- 3.0) days while excipient controls had a mean survival time of 17 (+/- 0.5) days. Similarly, at a dose of 200 micrograms rIL-1 beta/kg/d, mean survival was significantly (p less than 0.05) increased as compared to excipient controls (18.75 +/- 1.5 vs. 15.25 +/- 1.7 days, respectively). Daily injections of 400 micrograms/kg did not significantly increase the survival of glioma bearing animals, possibly as a consequence of rIL-1 beta toxicity at this dose.