C-reactive protein, leukocytes, and fever after central IL 1 and alpha-MSH in aged rabbits

Aged and young unanesthetized rabbits with intracerebroventricular cannulas were tested in experiments designed to determine whether increases in plasma C-reactive protein (CRP) level and leukocytosis can be rapidly induced by central administration of crude buffy-coat supernatant commonly called endogenous pyrogen or interleukin 1 (IL 1). The results indicate that both acute-phase responses occur during fever caused by central administration of this supernatant and that they are generally detectable within 2 h. Although the febrile response was smaller in aged female rabbits, there was no decline in CRP or leukocyte responses, an observation that was not predicted. The antipyretic neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) reduced fever caused by central IL 1 more effectively in the aged rabbits. alpha-MSH likewise inhibited the CRP and leukocyte responses to central IL 1. The results confirm that CRP and leukocyte responses can be driven by a central IL 1 signal and further indicate that the response can occur rapidly, consistent with direct central nervous system control of the acute-phase responses. The findings indicate that the acute-phase responses depend in part on the age of the host and that the responses can be modulated by an endogenous central nervous system peptide with known antipyretic and immune modulatory properties.