Acute-phase response to endogenous pyrogen in rabbit: effects of age and route of administration

Aspects of host defense, collectively called the acute phase response (APR), can be induced by central actions of cytokines. To determine whether aging alters this response, aged and young rabbits were given endogenous pyrogen (EP), a crude preparation containing interleukin 1 and other cytokines, via an intracerebroventricular cannula. Arterial blood was sampled before EP administration and 2, 4, and 24 h later. Measurements were made of changes in body temperature, white blood cells, neutrophils, concentration of antipyretic, anti-inflammatory peptide alpha-melanocyte stimulating hormone (alpha-MSH), corticosterone, and C-reactive protein (CRP) concentrations. EP caused greater fever and increases in corticosterone and CRP in young rabbits. EP-induced changes in circulating neutrophils did not show age-related differences. There was no significant change in alpha-MSH in either age group; thus only certain aspects of APR induced by central actions of EP were altered with aging. To determine whether changes in APR caused by peripherally administered cytokines are similar to those after central injection, young female rabbits were given EP by both routes. Although administration caused greater fever, increases in alpha-MSH and corticosterone concentrations and in neutrophil counts were greater after intravenous administration, perhaps the result of a combined influence on peripheral and central receptors. The EP-induced increase in circulating alpha-MSH is a new finding that indicates that this antipyretic and anti-inflammatory peptide is rapidly available to modulate host responses after challenge.