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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Saitoh
Minori
M
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan. saitoh_m@yamanouchi.co.jp
Taguchi
Katsunari
K
Momose
Kazuhiro
K
Suga
Kazutaka
K
Yamazaki
Noriyuki
N
Ono
Chizuko
C
Suzuki
Tatsuo
T
Takeuchi
Osamu
O
Yasuda
Shuhei
S
Miyata
Keiji
K
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001853:Bone Marrow / Q000187:drug effects; D016190:Carboplatin / Q000009:adverse effects*; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000188:drug therapy*; D017370:Interleukin-11 / Q000627:therapeutic use*; D051379:Mice; D011994:Recombinant Proteins / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017370:Interleukin-11; D011994:Recombinant Proteins; D016190:Carboplatin