Cytokines and Aggressive Behavior

Abstract

Studies conducted in rodents, primates and humans have provided evidence that proinflammatory cytokines may play an important in the regulation of aggression and rage behavior. More recent studies conducted in the cat have generated more direct evidence of cytokine involvement in modulating rage behavior. Activation of IL-I receptors in the medial hypothalamus and periaqueductal gray (PAG) potentiates defensive rage behavior in the cat. Facilitation of defensive rage is mediated through 5-HT2 receptors in the medial hypothalamus and PAG. Activation of IL-2 receptors in the medial hypothalamus and PAG differentially affect defensive rage behavior. In the medial hypothalamus, IL-2 receptors suppress defensive rage and this effect is mediated through GABAA receptors; in the PAG, IL-2 receptors facilitate the occurrence of defensive rage behavior and such effects are mediated through substance P NK1 receptors. With respect to peripheral mechanisms, LPS administration induces the release of a cascade of proinflammatory cytokines. Among the cytokines released, TNF-〈 appears to play a significant role in the induction of the suppressive effects of LPS upon defensive rage and in sickness behavior in the cat. Concerning the central mechanisms regulating LPS induced suppression of defensive rage and sickness behavior, serotonin 5-HT1A and PGE2 receptors in the medial hypothalamus appears to play key roles in controlling these processes.