Adrenalectomy enhances response of tumour necrosis factor-alpha (TNF-alpha) to haemorrhage in the conscious rat.
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.
Yamashita
M
M
Department of Emergency Medicine, University of Tsukuba School of Medicine, Tsukuba, Japan.
Yamashita
M
M
D000315:Adrenalectomy; D000818:Animals; D001143:Arousal; D001794:Blood Pressure / Q000276:immunology; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood; D006470:Hemorrhage / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood; D007262:Infusions, Intravenous; D007739:L Cells; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D011292:Premedication; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone