Administration of anti-IL-12 antibody in vivo inhibits rejection of a rat histiocytoma and suppresses cytokine response in a tumour-bearing host.

Activated macrophages are the major producers of heterodimeric cytokine interleukin-12 (IL-12). Earlier evidence suggested that early rejection of AK-5 tumours is mediated by IL-12 through interferon-gamma (IFN-gamma) production, involving activation of natural killer (NK) cells and upregulation of T-helper 1 (Th1)-type cytokine response. Injection of anti-IL-12 antibody into AK-5 tumour-bearing animals resulted in a large number of changes in the host immune response towards the tumour. These animals showed diminished NK-mediated antibody-dependent cell-mediated cellular cytotoxicity (ADCC) activity, down-regulation of Th1-type cytokine response, decreased anti-tumour antibody response ultimately leading to either delay or inhibition of the tumour-regression process. There was also increased production of IL-10 in the animals that had received anti-IL-12 antibody thereby resulting in the down-regulation of IL-2 and IFN-gamma production. IL-12 plays a major role in the activation of the different immune parameters responsible for early rejection of AK-5 tumour. We also studied the activation status of macrophages from tumour-transplanted animals and their ability to produce IL-12. Monocytes/macrophages from antibody-injected animals were less active and produced lower quantities of IL-12, IL-1 beta and tumour necrosis factor-alpha (TNF-alpha) as compared with the macrophages from AK-5 tumour-bearing animals.