Biomedical subjects

M M Coelho

Publications and source records attributed to M M Coelho.

21 records · Page 2Linked to original sources

PubMed1995

Multiple mechanisms mediate antipyretic action of glucocorticoids.

Glucocorticoids inhibit various components of the acute phase response, particularly the increase in body temperature (fever) induced by a variety of stimuli. In the present study these observations have been extended, and we have determined the effect of glucocorticoid treatment or surgical adrenalectomy on the cytokine and prostaglandin (PG) concentrations in plasma and cerebrospinal fluid (CSF) during the febrile response to endotoxin. Dexamethasone treatment, either before or after endotoxin injection, markedly inhibited fever and the increased plasma interleukin (IL)-6 and CSF IL-6, PGE2, and PGF2 alpha concentrations. Adrenalectomized (ADX) rats showed higher fevers and plasma and CSF IL-6, PGE2, and PGF2 alpha, concentrations compared with sham-operated animals and exhibited a lower plasma-to-CSF IL-6 ratio than sham-operated animals. Dexamethasone pretreatment also inhibited fever induced by centrally injected TNF-alpha, IL-1 beta, or IL-6. Pyrogenic response to IL-8 was not modified by indomethacin but was markedly inhibited by prior treatment with dexamethasone. These results support the hypothesis that endogenous glucocorticoids function as part of an inhibitory feedback system involved in the modulation of fever and that multiple mechanisms may be involved in their antipyretic effect.

Adrenalectomy↗

PubMed1993

Dexamethasone inhibits the pyrogenic activity of prostaglandin F2 alpha, but not prostaglandin E2.

The effect of dexamethasone on prostaglandin (PG) E2- and PGF2 alpha-induced fever was studied in rats. Intracerebroventricular injection of PGE2 and PGF2 alpha (500 ng) induced increases in body temperature (maximal temperature rises of 0.97 +/- 0.13 degrees C and 0.78 +/- 0.18 degrees C, respectively, vs. vehicle 0.12 +/- 0.09 degrees C) of unrestrained rats maintained within the thermoneutral zone. PGE2-induced fever peaked earlier and the defervescence was faster when compared to the response induced by PGF2 alpha. Subcutaneous pre-administration of dexamethasone (0.5 mg/kg) did not affect PGE2-induced fever (maximal temperature rise of 1.00 +/- 0.08 degrees C), but completely prevented the pyrogenic activity of PGF2 alpha (maximal temperature rise of 0.16 +/- 0.16 degrees C). Neither PGE2- nor PGF2 alpha-induced fever was significantly altered (maximal temperature rises of 0.90 +/- 0.11 degrees C and 0.64 +/- 0.14 degrees C, respectively) by intraperitoneal administration of indomethacin (2 mg/kg). These results demonstrate for the first time that glucocorticoids, in addition to inhibiting endotoxin- and cytokine-induced fever, can also modulate the pyrogenic activity of some prostaglandins, possibly via suppression of the synthesis of corticotropin-releasing factor, indicating that multiple mechanisms may be involved in the antipyretic activity of these steroids.

Animals↗

PubMed1992

Endotoxin-induced fever is modulated by endogenous glucocorticoids in rats.

This study was designed to determine if the febrile response, similar to the inflammatory response, can be modulated by endogenous glucocorticoids. A single intraperitoneal injection of lipopolysaccharide (LPS, 200 micrograms/kg) induced a significant increase in rectal temperature of unrestrained rats maintained within the thermoneutral zone. The febrile response was fully abolished following treatment with a glucocorticoid, dexamethasone (DEX), but was not affected by a mineralocorticoid, deoxycorticosterone acetate (DOCA). Adrenalectomized (ADX) rats were markedly more sensitive to the lethal effects of LPS (200 micrograms/kg), such that all the animals died during the course of the experiment. In addition, ADX rats showed an enhanced febrile response to LPS (10 micrograms/kg ip) in comparison with sham-operated or adrenal-demedullated rats. This enhanced response was reduced by chronic or acute treatment with DEX, but not DOCA. LPS (10 micrograms/kg) also induced a marked rise in plasma corticosterone levels in control rats. In contrast, ADX rats displayed very low plasma corticosterone levels, which were not changed by LPS. In conclusion, the present results reveal that endogenous glucocorticoids are important modulators of LPS-induced fever.

Adrenalectomy↗