Recombinant human interleukin-11 improved carboplatin-induced thrombocytopenia without affecting antitumor activities in mice bearing Lewis lung carcinoma cells.

Abstract

Interleukin-11 (IL-11) is a stromal cell derived multifunctional cytokine, which plays important roles in the hematopoietic and nonhematopoietic systems. Recombinant human IL-11 (rhIL-11) is used in the treatment of chemotherapy-induced thrombocytopenia. We have investigated the effects of rhIL-11 on the antitumor activity of chemotherapeutic agents and on thrombocytopenia in myelosuppressed mice bearing tumor cells. We tested the effect of rhIL-11 on Lewis lung carcinoma (LLC) cell proliferation when used alone or in combination with three antitumor agents in vitro. Also, a newly developed chemotherapy-induced myelosuppressed mice model bearing LLC cells was used to study the effects of rhIL-11 on the antitumor activity and on thrombocytopenia. On its own, rhIL-11 (1-100 ng/ml) did not stimulate cell proliferation, and did not alter the antitumor activities of carboplatin, mitomycin C, or etoposide in vitro. In mice implanted with LLC cells (1 x 10(4)), carboplatin (50 mg/kg/day for 2 consecutive days, i.p.) inhibited tumor growth and caused thrombocytopenia. Treatment with rhIL-11 (500 microg/kg/day, from the day following the last dosing with carboplatin for 14 days, s.c.) successfully prevented thrombocytopenia without affecting the antitumor activity of carboplatin. With rhIL-11 there was no obvious effect on the red blood cell count, white blood cell count, or body weight. These results support the assertion that rhIL-11 may be a significant therapeutic agent for thrombocytopenia following cancer chemotherapy, and that it need be associated with little fear of tumor proliferation.