Interaction of interleukin-11 with cytotoxic therapies in vitro against CEM cells and in vivo against EMT-6 murine mammary carcinoma.
Interleukin-11(rhIL-11) is a cytokine that has been shown to enhance the recovery of bone marrow and intestinal crypt cells after cytotoxic insult with radiation or anticancer drugs. The current study examined the effects of rhIL-11 on the response of CEM human lymphoblastic leukemia cells and on the EMT-6 murine mammary carcinoma in vivo to cytotoxic anticancer therapies. Exposure of CEM cells to rhIL-11 for 24 hr did not alter the cytotoxicity of melphalan or radiation, increased the cytotoxicity of CDDP (100 muM) and 4-hydroperoxycyclophosphamide (50 betaM) and decreased the cytotoxicity of 5-fluorouracil and ara-C toward the cells. Treatment of mice bearing the EMT-6 tumor with rhIL-11 twice daily for 4 days prior to and the day of cytotoxic therapy resulted in no significant change in the tumor cell killing or bone marrow CFU-GM killing by melphalan, cyclophosphamide, thiotepa, CDDP, radiation, 5-fluorouracil or ara-C. Administration of rhIL-11 twice per day on days 7-18 to EMT-6 tumor bearing animals receiving high dose chemotherapy (melphalan, thiotepa or cyclophosphamide) as a single dose on day 7 followed by mobilized peripheral blood cells on day 8 and rhG-CSF on days 8-20, tended to prolong the tumor growth delay produced by the drugs. This rhIL-11 treatment also resulted in a more rapid recovery of white blood cells and granulocytes in the animals. Furthermore, animals treated with rhIL-11 had improved survival rates compared with animals receiving all other normal tissue support without rhIL-11.
Teicher
B A
BA
Dana-Farber Cancer Institute and Joint Center for Radiation Therapy, Boston, USA.
Chen
Y N
YN
Ara
G
G
Emi
Y
Y
Kakeji
Y
Y
Maehara
Y
Y
Keyes
S
S
Northey
D
D
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004347:Drug Interactions; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D017370:Interleukin-11