PMID- 12430001 OWN - NLM STAT- MEDLINE DCOM- 20030514 LR - 20041117 IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 10 IP - 6 DP - 2002 Dec TI - Interleukin-12-mediated induction of systemic immunity in the periphery and recruitment of activated T cells into the brain produce limited antitumor effects compared with interleukin-2. PG - 741-7 AB - Interleukin-12 (IL-12) stimulates the type 1 helper T (Th1) cell responses and augments antitumor immunity. We examined possible antitumor effects of IL-12 secreted intracerebrally (i.c.) and/or subcutaneously (s.c.) in an experimental glioblastoma model and compared the effects with those of IL-2. Rat 9L gliosarcoma cells retrovirally transduced with the IL-12 or IL-2 gene (9L/IL-12 and 9L/IL-2, respectively) were completely rejected when they were s.c. inoculated. The transduced cells, implanted i.c., developed progressive brain tumors at reduced rates compared with 9L brain tumors and the growth retardation of 9L/IL-2 tumors was greater than that of 9L/IL-12 tumors. When rats were s.c. immunized with either 9L/IL-12 or 9L/IL-2 cells, the growth of 9L brain tumors developed in the rats was suppressed compared with that of 9L tumors in naive rats. Among various combinations of simultaneous inoculations of cytokine producers s.c. and i.c., 9L/IL-2 but not 9L/IL-12 cells inoculated i.c. were rejected when the rats were s.c. immunized with either 9L/IL-12 or 9L/IL-2 cells. The synergistic antitumor effects induced were correlated with the infiltration levels of CD8+ and CD4+ T cells into brain tumors. Tumor-specific cytotoxic activity was induced in the rats immunized s.c. with 9L/IL-2 but not fully in the rats with 9L/IL-12 cells. These results collectively suggest that the antitumor activity with IL-2 was superior to IL-12 both in the induction of cytotoxic T cells and in the recruitment of activated T cells into brain tumors. FAU - Iwadate, Yasuo AU - Iwadate Y AD - Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan. iwadate@med.m.chiba-u.ac.jp FAU - Namba, Hiroki AU - Namba H FAU - Sakiyama, Shigeru AU - Sakiyama S FAU - Yamaura, Akira AU - Yamaura A FAU - Tagawa, Masatoshi AU - Tagawa M LA - eng PT - Journal Article PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antineoplastic Agents) RN - 0 (Interleukin-2) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Adjuvants, Immunologic/*pharmacology MH - Animals MH - Antineoplastic Agents/*pharmacology MH - Brain Neoplasms/*drug therapy MH - Cell Movement/drug effects MH - Humans MH - Immunity/drug effects MH - Interleukin-12/*pharmacology MH - Interleukin-2/*pharmacology MH - Mice MH - Rats MH - T-Lymphocytes/drug effects MH - Transduction, Genetic EDAT- 2002/11/14 04:00 MHDA- 2003/05/15 05:00 CRDT- 2002/11/14 04:00 PHST- 2002/11/14 04:00 [pubmed] PHST- 2003/05/15 05:00 [medline] PHST- 2002/11/14 04:00 [entrez] PST - ppublish SO - Int J Mol Med. 2002 Dec;10(6):741-7.