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

Abstract

SUMMARY Several factors have been implicated in TNF-α induction after haemorrhage, but the precise mechanism is unknown. To assess a possible role of adrenal glands on TNF-α 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-α 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-α mRNA showed rapid increases after haemorrhage in the Sham group, and these increases were significantly augmented in the ADX group. Pretreatment with CS (100 μg/h) negated these augmentations in ADX rats. These results show that adrenalectomy enhances the response of TNF-α to 20 ml/kg haemorrhage in the conscious rat, and suggest that endogenous glucocorticoids may play an inhibitory role in the induction of TNF-α after haemorrhage.