The effects of systemic and intratumoral interleukin-12 treatment in C6 rat glioma model.

Objective: Cytokine based immunotherapy has long been an exciting field for many investigators aiming to provide an effective alternative treatment modality for glioma management. Among these cytokines, interleukin-12 (IL-12) plays a crucial role in mediating inflammatory and antitumoral activity on the host defence. We have investigated the therapeutic role of systemic and local delivery of IL-12 in C6 rat glioma model and compared these two modalities. Methods: The donor C6 glioma cells were injected stereotactically to 32 Wistar rats and right frontal tumor formation was established in all subjects. The rats were evenly divided into four groups as intratumoral (i.t.) control group (Group IA), intraperitoneal (i.p.) control group (Group IB), i. t. treatment group (Group II) and i.p. treatment group (Group III). Magnetic resonance imaging were performed to 12 rats (three from each group) on the seventh post-inoculation day. Recombinant mouse IL-12 (rmIL-12) was administered via i.t. (0.1 mg 5 ml/day/rat) and i. p. (0.1 mg 20 ml/day/rat) routes to treatment groups between days 9 and 11 following tumor inoculation, for 3 consecutive days. The rats which were unresponsive to the external stimuli, unable to feed themselves or having severe neurological impairment were decapitated and the specimens were histopathologically examined. Results: The subjects of Group III (i.p.) showed a statistically significant prolongation in survival time (mean=39 days) when compared to the control group (mean=31.7 days) (p=0.035) and Group II (i.t.) (mean=24.5 days) (p=0.005). Histopathologic examination of Group III revealed markedly increased intratumoral and peritumoral lymphocyte infiltration compared with the other groups. Conclusion: This study demonstrated that systemic administration of IL-12 in C6 glioma model in rats prolongs the survival, probably by stimulating the cellular immunity leading to lymphocytic infiltration.