Role of the central nervous system in acute-phase responses to leukocytic pyrogen.

Intracerebroventricular injection of rabbit leukocytic pyrogen (LP) into conscious, healthy cannulated rabbits produced markedly enhanced febrile and acute-phase responses as compared with equivalent-dose, single bolus intravenous injection. The increased effectiveness in inducing granulocytosis and hypoferremia on intracerebroventricular injection was matched by changing the method of administration of intravenous LP from a single initial bolus to multiple fractional doses over a 2-h period. This suggested that augmentation for these parameters may have reflected only a "reservoir" function of the cerebral ventricles which prevented rapid clearance of LP from the blood. The ability of LP to induce hepatic synthesis of haptoglobin and C-reactive protein was so markedly enhanced by intracerebroventricular injection, however, that a role of the central nervous system in mediating or in modifying in an important way a non-neural mechanism for this mediation must be postulated.