Antileukocyte activity I. Systemic inhibition of cellular emigration following local inflammation

Inflammation in progress at one site decreases edema formation at a second and separate inflammatory focus. This clinically important phenomenon is known as counter-irritation. Since its effect on leukocyte responses has not been defined, we investigated in rats the systemic anti-inflammatory effect of local irritant injection on cellular emigration, particularly monocytes. Macrophage accumulation at a subcutaneous inflammatory site was severely depressed by prior intraperitoneal irritant injection despite continued macrophage accumulation in the peritoneal cavity and normal circulating monocyte levels. The phenomenon also existed in the peritoneal cavity to subcutaneously administered irritants and involved PMNs as readily as macrophages. Anti-inflammation occurred only when the counter-irritant was injected before or simultaneously with the measured inflammatory response while the degree and duration of inhibition depended upon the nature and amount of counter-irritant injected. These studies demonstrate that local inflammation inhibits leukocyte reactivity. Transplantation of syngeneic tumor but not normal cells also produced a depression in macrophage inflammatory responses. This inhibition differed from counter-irritation by not affecting granulocytes and by being transient despite tumor persistence.