E-type prostaglandins and interferons: yin-yang modulation of macrophage tumoricidal activity

Abstract

It is proposed that nonimmunologic microenvironmental stimuli such as interferons and E-type prostaglandins (PGE) can modulate macrophage tumoricidal activity in local tissue immunity. These agents act as "local hormones" since they have a high catabolic rate and short biologic half-life in serum. Interferons provide a common pathway for induction of cytotoxic macrophages by diverse agents such as viruses, bacterial lipopolysaccharides, and double-stranded RNA, and PGE act as a biologic "resistor" to control expression of activated macrophage tumor killing. Since both PGE and interferons are secretory products of activated macrophages, it is envisioned that they could act in negative and positive feedback mechanisms to intrinsically modify macrophage functional activity. Finally, tumors may defend themselves from attack by activated tumoricidal macrophages by releasing high levels of PGE that subvert local macrophage activity.