COINCIDENTAL CHANGES IN BEHAVIOR AND PLASMA-CORTISOL IN UNRESTRAINED PIGS AFTER INTRACEREBROVENTRICULAR INJECTION OF TUMOR-NECROSIS-FACTOR-ALPHA

The coincidental behavioral and physiological responses to inflammator y stimuli administered either peripherally or centrally were evaluated . In the first study, twenty castrated male pigs were injected ip with 0, 0.5, 5, or 50 mu g/kg BW lipopolysaccharide (LPS). Body temperatur e was monitored telemetrically, and serial blood samples were collecte d via an indwelling jugular catheter for determination of plasma corti sol and tumor necrosis factor-alpha (TNF-alpha) concentrations. Sickne ss behaviors were measured during 10-min tests at 0, 2, 4, 8, 12, and 24 h post injection. The 5 and 50 mu g/kg doses of LPS increased plasm a concentrations of cortisol and TNF-alpha, while inducing anorexia, h ypersomnia, and fever. In contrast, although 0.5 mu g/kg LPS induced a cute anorexia, hypersomnia, and fever, it did not increase plasma TNF- alpha; and the cortisol response was small and transient, suggesting t he behavioral system in pigs is more responsive to LPS than the hypoth alamic-pituitary-adrenal (HPA) axis. Be cause LPS-induced behavior and activation of the HPA axis involve proinflammatory cytokines in the b rain, in a second study, unrestrained pigs with jugular catheters were injected intracerebroventricularly (ICV) with recombinant porcine TNF -alpha. Vehicle or TNF-alpha (0, 5, or 50 ng/kg) was injected ICV, and plasma cortisol and behavior were determined as before. Pigs injected ICV with 50 ng/kg TNF-alpha showed anorexia, hypersomnia, and an abru pt increase in plasma cortisol concentration. Whereas 5 ng/kg TNF-alph a ICV also induced marked sickness behavior, it failed to stimulate th e HPA axis, as indicated by plasma cortisol levels. That there was a d istinct difference in the magnitude of behavioral and endocrine respon ses to LPS and TNF-alpha suggests that different systems that are resp onsive to inflammatory stimuli exhibit different sensitivities.