Adrenalectomy enhances response of tumour necrosis factor-alpha (TNF-alpha) to haemorrhage in the conscious rat

Abstract

Several factors have been implicated in TNF-alpha induction after haemorrhage, but the precise mechanism is unknown. To assess a possible role of adrenal glands on TNF-alpha induction after haemorrhage, adrenalectomized (ADX) and sham-adrenalectomized (Sham) rats were subjected to 20 ml/kg haemorrhage (approximately 30% of the total blood volume) over 5 min in the conscious state, and changes in serum TNF and hepatic TNF-alpha mRNA were analysed by cytotoxicity against L929 cells and by semiquantitative reverse transcription-polymerase chain reaction, respectively. Changes in plasma corticosterone (CS) and mean arterial blood pressure (MABP) were also detected. Plasma CS levels showed a rapid increase after haemorrhage in Sham rats, whereas there was no response in ADX rats. Responses of MABP were comparable in the two groups. Both serum TNF and hepatic TNF-alpha mRNA showed rapid increases after haemorrhage in the Sham group, and these increases were significantly augmented in the ADX group. Pretreatment with CS (100 microg/h) negated these augmentations in ADX rats. These results show that adrenalectomy enhances the response of TNF-alpha to 20 ml/kg haemorrhage in the conscious rat, and suggest that endogenous glucocorticoids may play an inhibitory role in the induction of TNF-alpha after haemorrhage.

Fig. 1

Time course of changes in plasma corticosterone (CS) levels (a) and mean arterial blood pressure (MABP; b). Values are mean ± s.d. (n = 5). *P < 0·05 between Sham (•) and adrenalectomized (ADX; ▪) rats by anova.

Fig. 2

Time course of changes in hepatic TNF-α mRNA (a) and serum TNF (b) after 20 ml/kg × 5 min haemorrhage. TNF-α mRNA is expressed as relative multiple increase compared with normal untreated rats. Values are mean ± s.d. (n = 5). *P < 0·05 between Sham (•) and adrenalectomized (ADX; ▪) rats by anova.

Fig. 3

Plasma corticosterone (CS) (a), hepatic TNF-α mRNA (b), and serum TNF (c) levels 1 h after 20 ml/kg × 5 min haemorrhage in adrenalectomized (ADX) rats pretreated with various doses of CS (0, 3, 10, and 100 μg/h). Values are mean ± s.d. (n = 5). *P < 0·05 versus vehicle (0 μg/h) by Tukey's test after anova.