Interleukin-1beta and tumor necrosis factor-alpha mediation of endotoxin action on growth hormone.
In humans and sheep, endotoxin (LPS) administration results in increased growth hormone (GH) concentrations. To determine the role of cytokines in the effect of LPS on GH, sheep were challenged with IL-1beta or TNF-alpha. GH data were compared with results with LH, where the major effects of LPS are known to act via the hypothalamus. Intracerebroventricular (icv) administration of IL-1beta or TNF-alpha did not alter plasma concentrations of GH. Endotoxin was then administered intravenously (iv) in combination with icv injection of IL-1 receptor antagonist (IL-1RA), TNF antagonist (sTNF-R1), or saline. Administration of LPS increased GH (P < 0.0001), although coadministration of IL-1ra or sTNF-R1 icv did not alter GH response to LPS. In contrast, plasma concentrations of LH were profoundly inhibited by icv administration of either cytokine (P < 0.03), but the LH response to LPS was not altered by cytokine antagonists. Intravenous administration of either IL-1beta or TNF-alpha increased plasma concentrations of GH (P < 0.0001). Administration of IL-1RA and sTNF-R1 iv prevented LPS-induced increases in GH. Although LH was suppressed by high iv doses of IL-1beta (P = 0.0063), the antagonists did not alter the LH response to LPS. To determine whether LPS might directly activate GH release, confocal microscopy revealed colocalization of CD14, the LPS receptor, with GH and, to a lesser extent, LH and some prolactin (PRL)-containing cells, but not ACTH or TSH. These data are consistent with the effects of LPS on GH secretion originating through peripheral cytokine presentation to the pituitary, as well as a potential to act directly on selective populations of pituitary cells via CD14.
Daniel
J A
JA
Animal and Range Sciences, South Dakota State University, Brookings, South Dakota, USA.
Elsasser
T H
TH
Martínez
A
A
Steele
B
B
Whitlock
B K
BK
Sartin
J L
JL
D000818:Animals; D016207:Cytokines / Q000097:blood*; D013006:Growth Hormone / Q000097:blood*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007986:Luteinizing Hormone; D013006:Growth Hormone