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

Abstract

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.

Inflammation and remodelling in the ageing airway

“…In a rabbit model of sepsis examining neutrophil and corticosterone levels, no significant differences in age response were identified 17 . Alveolar macrophages from senescent animals capable of generating reactive oxygen species and nitric oxide showed a significantly impaired response to lipopolysaccharide (LPS) stimulation compared with healthy adult controls 18 .…”

Fever and feeding in the rat: Actions of intrahypothalamic interleukin‐6 compared to macrophage inflammatory protein‐1β (MIP‐1β)

“…, 1988;Mifiano et al, 1990;Myers et al, 1976;Ruwe and Myers, 1982). Since these substances may mimic, in part, the central effect on T, of a bacterial pyrogen, they are thought to be involved in the acute phase response of which thermogenesis is a cardinal component (Blatteis et al, 1990;Martin et a]., 1989;Myers, 1980). For example, an interleukin such as IL-1 injected into the AH/ POA evokes a dose-dependent fever in several species (Chance and Fischer, 1991), which parallels the response to an endotoxin applied similarly to the same diencephalic region (Myers et al, 1974;Villablanca and Myers, 1965).…”

Alpha‐melanocyte‐stimulating hormone suppresses fever and increases in plasma levels of prostaglandin E2 in the rabbit.

“…administration of endotoxin (Martin & Lipton, 1990) and i.v. administration of endogenous pyrogen (EP) (Martin, Deeter & Lipton, 1989). It has been proposed that endogenously produced a-MSH may have a role in limiting the febrile response to pyrogens.…”