Activation of macrophage function by intraperitoneal administration of the streptococcal antitumor agent OK-432.

Motility, adhesiveness, IL1 production, and inhibition of tumor cell growth in vitro were examined in murine peritoneal macrophages obtained after intraperitoneal injection of a streptococcal preparation OK-432, heat-inactivated OK-432 (HI-OK-432), and thioglycollate medium (TG). By varying the interval between intraperitoneal injection of OK-432 and the harvest of peritoneal macrophages, it was found that OK-432 induced a time-dependent multi-step alteration of these properties: step I increased motility on day 1: step II increased adhesiveness on day 2; and step II increased inhibition of tumor cell growth and IL1 production. During step III, the peritoneal macrophage population, including Ia-bearing cells, increased dramatically in the peritoneal cavities of OK-432-treated mice. In contrast, injection of either HI-OK-432 or TG, which lack antitumor activity in vivo, initiated steps I and II, but not step III. The Ia-bearing macrophages induced by OK-432 showed high ability of IL1 production, but low growth inhibitory activity against tumor cells. Based on these results, OK-432 seems to be performing a dual function: eliciting a new population of macrophages to the site of injection (heat stable function), and inducing two different populations of antitumor macrophages and Ia-bearing macrophages (heat unstable function).