Endotoxin induced increases in rat plasma pituitary-adrenocortical hormones are better reflected by alterations in tumor necrosis factor alpha than interleukin-1beta.
In order to assess the relative cytokine contribution to endotoxin stimulation of pituitary-adrenocortical hormone secretion, we measured plasma levels of interleukin-1beta (IL-1beta), tumor necrosis factor (TNF alpha), adrenocorticotropin (ACTH) and corticosterone following lipopolysaccharide (LPS) challenge in rats. LPS administration induced robust increases in both plasma ACTH and corticosterone levels at 3 h after i.p. injection; while ACTH decreased towards control levels, corticosterone remained at peak concentrations at 6 h after LPS injection. Basal levels of plasma IL-1beta were below the sensitivity of the ELISA and basal levels of plasma TNF alpha were 0.25+/-0.12 pM. Small but highly variable non-significant increases in plasma IL-1beta levels were seen at 3 h and 6 h after injection of LPS. The lack of functional consequences of the small increases in IL-1beta levels was demonstrated by unchanged levels of [125I]IL-1alpha binding in liver at 3 h after LPS injection. In contrast, dramatic increases in plasma TNF alpha concentrations were observed at 3 h and decreased to non-injected control levels at 6 h after LPS injection. There was a significant positive correlation between ACTH and TNF alpha after LPS injection, while no correlation was seen between ACTH and IL-1beta. These data demonstrate differential regulation of IL-1beta and TNF alpha by endotoxin treatment and suggest that TNF alpha may be a more potent mediator of LPS-induced ACTH secretion in rat.
Takao
T
T
Second Department of Internal Medicine, Kochi Medical School, Japan. takaot@dtn.am400gw.kochi-ms.ac.jp
Nanamiya
W
W
Takemura
T
T
Nishiyama
M
M
Asaba
K
K
Makino
S
S
Hashimoto
K
K
De Souza
E B
EB
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone