Tumor necrosis factor-alpha is a potent ACTH secretagogue: comparison to interleukin-1 beta.
Tumor necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1) are secreted by activated monocytes and other immune cells. Since IL-1 has been shown to elevate rat plasma ACTH and both of these cytokines induce similar acute-phase responses, the present studies of TNF were undertaken to characterize the ACTH response to this immune cell product. Human rTNF, administered iv at doses (100-1000 ng) which failed to affect blood pressure, food consumption or prolactin levels, resulted in significant peak elevations of rat plasma ACTH within 20 min (mean +/- SE 304 +/- 94 and 958 +/- 128 pg/ml for 100 and 1000 ng, respectively, compared to 53 +/- 16 pg/ml for vehicle). rTNF from two different sources produced similar elevations of ACTH as an equivalent amount of rIL-1. TNF failed to affect cultured anterior pituicytes, and it did not modify the response to CRF. When administered into the upper third cerebroventricle, TNF 20 ng failed to affect ACTH levels whereas IL-1 30 ng raised ACTH to 638 +/- 79 pg/ml compared to 177 +/- 24 pg/ml for vehicle (p less than .001). Furthermore, intraparenchymal injection of IL-1, directly above the median eminence, elevated ACTH to 484 +/- 93 pg/ml; again, TNF was completely ineffective. Thus, TNF-alpha and IL-1 beta are both potent ACTH secretagogues with complementary modes of action; however, the proximate target of TNF action appears to be peripheral to the CNS and pituitary whereas that of IL-1 appears to be the median eminence.
Sharp
B M
BM
Endocrine-Neuroscience Research Lab, Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.
Matta
S G
SG
Peterson
P K
PK
Newton
R
R
Chao
C
C
Mcallen
K
K
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007263:Infusions, Parenteral; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000324:Adrenocorticotropic Hormone