Antileukocyte activity II. Induction of tolerance to systemic anti-inflammation associated with local irritation and major surgery.

Anergy associated with cancer or major surgery may derive from the systemic antileukocyte effect induced by local inflammatory reactions (counter-irritation). Since the mechanism of the latter phenomenon is unknown, we approached the problem by asking if tolerance develops to repeated local irritant injections. Our results demonstrate that both tolerance and cross-desensitization occur rapidly to inflammatory agents (inflammagens) such as proteose peptone, thioglycollate, and carrageenan but not to the mitogens Con A, PHA-P, or LPS which also induce local inflammation. We interpret this data as supporting the notion that a common mechanism underlies the counter-irritant action of inflammagens but that injection of mitogens induces an additional mechanism of anti-inflammation distinguished from the former by its lack of tolerance induction. Based upon cross-desensitization experiments, we show that the anti-inflammatory effect of surgical amputation is analogous to that induced by inflammagens. In contrast, the systemic anti-inflammatory effect of tumor bearing, like that induced by mitogens, resists cross-desensitization suggesting that its mediation is not caused solely by the mechanism common to the counter-irritant action of inflammagens or major surgery.