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

1989 ◽  
Vol 257 (1) ◽  
pp. R189-R193
Author(s):  
L. W. Martin ◽  
L. B. Deeter ◽  
J. M. Lipton

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.

1981 ◽  
Vol 63 (1) ◽  
pp. 164-176 ◽  
Author(s):  
Marcelo B. Sztein ◽  
Stefanie N. Vogel ◽  
Jean D. Sipe ◽  
Patrick A. Murphy ◽  
Steven B. Mizel ◽  
...  

1987 ◽  
Vol 252 (1) ◽  
pp. E27-E32 ◽  
Author(s):  
S. E. Goldblum ◽  
D. A. Cohen ◽  
M. Jay ◽  
C. J. McClain

The mechanism(s) of stress-induced hypoferremia and hypozincemia remains unclear. We studied the role of granulocytes and lactoferrin (LF) in endotoxin and murine interleukin 1 (IL-1)-induced depression of serum Fe and Zn concentrations in both rabbits and rats. Both endotoxin and IL-1 administration induced significant hypoferremia (P less than 0.01) and hypozincemia (P less than 0.01) after 6 h in both species. Granulocyte depletion before IL-1 infusion significantly (P less than 0.01) diminished the hypoferremia but not the hypozincemia. Moreover, infusion of 5 or 15 mg of human LF into rabbits caused significant hypoferremia (P less than 0.005) without hypozincemia. Significant hypozincemia (P less than 0.01) could only be demonstrated after a 75-mg infusion. In contrast, infusions of human transferrin at equivalent doses (5, 15, and 75 mg) induced neither hypoferremia nor hypozincemia. Therefore endotoxin and IL-1-induced hypoferremia and, to a much lesser degree, hypozincemia are granulocyte dependent. Granulocyte released LF is a specific carrier molecule for transport and removal of Fe from the circulation during the acute phase response. The data suggest a mechanistic dissociation of IL-1-induced hypoferremia and hypozincemia with LF-independent mechanisms for Zn.


2010 ◽  
Vol 24 (4) ◽  
pp. 381-395 ◽  
Author(s):  
N. Venteclef ◽  
T. Jakobsson ◽  
A. Ehrlund ◽  
A. Damdimopoulos ◽  
L. Mikkonen ◽  
...  

1993 ◽  
Vol 11 (1) ◽  
pp. 31-36 ◽  
Author(s):  
P Hagan ◽  
S Poole ◽  
A F Bristow

ABSTRACT Regulation of a number of aspects of the acute-phase response, including induction of fever and activation of the hypothalamo-pituitary-adrenal axis, occurs within the hypothalamus. The acute-phase response appears to be co-ordinated by the inflammatory cytokine interleukin-1 (IL-1). A number of studies using hybridization techniques to measure IL-1 gene expression and immunocyto-chemistry to localize immunoactive IL-1 have established the concept that the central nervous system, and in particular the hypothalamus, is a site of IL-1 production, and that levels increase in response to inflammatory stimuli. In this report we present data on the levels of IL-1β produced in the rat hypothalamus using quantitative immunoassay techniques. Bacterial endotoxin, administered to rats in vivo, evoked increases in hypothalamic IL-1β levels which were significant within 1 h, and reached maximum levels at 5–10 h. The response to endotoxin was dose-related, and levels reached in hypothalamic extracts corresponded to intra-hypothalamic levels of the order of 20 ng/ml. During short-term in-vitro culture of rat hypothalami, endotoxin stimulated a dose-related increase in both the synthesis and the secretion of IL-1β, which reached similar levels to those seen after in-vivo stimulation. Hypothalami obtained from animals stimulated with endotoxin in vivo did not, however, show any evidence of persistent stimulation of IL-1β production when subsequently cultured in vitro. These data support the concept that production of hypothalamic IL-1 is an essential step in regulating the activity of the hypothalamus during the acute-phase response, and provide for the first time quantitative data on the magnitude, dose—response relationships and time-courses of rat hypothalamic IL-1β production in vivo and in vitro.


1991 ◽  
Vol 81 (5) ◽  
pp. 677-683 ◽  
Author(s):  
Lindsay M. Weight ◽  
Donald Alexander ◽  
Peter Jacobs

1. It has been suggested that the physiological consequences of strenuous exercise are analogous to those of the acute-phase response. 2. In 70 male and 20 female competitive distance runners, a marked, but transient, neutrophil leucocytosis occurred immediately after these athletes completed a standard (42 km) marathon race. Concomitant significant increases were noted in the plasma cortisol levels, creatine kinase activity, C-reactive protein level, total protein level and albumin level (P <0.01). 3. The plasma fibrinogen, C-reactive protein and total protein concentrations were markedly increased both 24 h and 48 h after exercise (P <0.01). The serum haptoglobin level was significantly decreased after exercise (P <0.01), and increased 48 h later (P <0.05). There was no change in the serum iron level, total iron-binding capacity, per cent saturation of transferrin and serum ferritin level. 4. A significant increase in interleukin-1-type activity was demonstrated immediately and 24 h after exercise (P <0.01). 5. It is concluded that the metabolic sequelae of sustained exercise are similar, but not analogous, to the acute-phase response, and interleukin-1 probably plays a significant role in linking the haematological and immunological changes observed after sustained strenuous exercise.


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