Received July 7, 2004
Revised August 5, 2004
Accepted after revision September 21, 2004
Pregnancy Influences the Plasma Cytokine Response to Intraperitoneal Administration of Bacterial Endotoxin in Rats
Anita E. Fofie 1,
James E. Fewell 1*,
Sherry L. Moore 1
1 University of Calgary
* To whom correspondence should be addressed. E-mail: fewell{at}ucalgary.ca.
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Abstract |
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Rats have an attenuated febrile response to intraperitoneal (i.p.) administration of exogenous pyrogen (e.g. bacterial endotoxin) near the term of pregnancy. To investigate possible mechanisms of this unique thermoregulatory response, the present experiments were carried out on 18 nonpregnant and 16 near-term pregnant Sprague-Dawley rats to test the hypothesis that pregnancy alters the balance of pyrogenic cytokines and antipyretic and/or cryogenic (antipyretic/cryogenic) cytokines in response to exogenous pyrogen. To test our hypothesis, we measured plasma levels of IL-1
,IL-6, IL-1ra, and TNF at two and four hours following i.p. administration of 160 µg/kg E. coli LPS (i.e., EC100 dose or the smallest dose that elicits a maximal febrile response in nonpregnant rats) in nonpregnant as well as in day 20 gestation pregnant rats (term ~21 days). In nonpregnant rats, E. coli LPS elicited statistically significant increases in plasma concentrations of IL-1, IL-6, IL-1ra and TNF as compared to that observed following vehicle. In pregnant rats, however, E. coli LPS elicited statistically significant increases in antipyretic/cryogenic cytokines (i.e., IL-1ra & TNF) but not in pyrogenic cytokines (i.e., IL-1, & IL-6). Thus, a differential pyrogenic and antipyretic/cryogenic plasma cytokine response may mediate in part the attenuated febrile response to exogenous pyrogen observed in rats near the term of pregnancy.
Key Words:
Cytokine, Fever, Pregnancy
