Interleukin 6 production in fetal rat long bone cultures is correlated with PGE2 release and does not correlate with the extent of bone resorption.
Reports from several laboratories have suggested that interleukin 6 (IL-6) may play a role in the process of bone resorption. We have extended these studies by examining the role of IL-6 in fetal rat long bone (FRLB) resorption stimulated by a variety of agents, including parathyroid hormone (PTH); 1,25 dihydroxyvitamin D3 (1,25(OH)2D3); interleukin 1 (IL-1); tumour necrosis factor alpha (TNF-alpha) and lipopolysaccharide (LPS). This model of bone resorption does not require the generation of osteoclasts in order to elicit a resorptive response and allowed us to assess whether IL-6 can directly affect osteoclastic bone resorption. We confirmed previous studies which showed that exogenous recombinant murine or human IL-6 does not stimulate bone resorption and demonstrated that IL-6, when added prior to the addition of parathyroid hormone, caused a significant but somewhat variable inhibition at 120 hours. Exogenous PGE2 stimulated both IL-6 production and resorption in FRLB cultures in a concentration-dependent manner. Endogenous production of IL-6 in fetal rat long bone (FRLB) cultures was stimulus dependent and generally correlated with prostaglandin E2 (PGE2) levels in the same cultures. However, endogenous IL-6 production did not correlate with the extent of bone resorption, except when IL-1 and PGE2 were used as stimuli. Addition of indomethacin and diclofenac to IL-1 stimulated cultures demonstrated that both the IL-6 production and bone resorption were largely PGE-2 dependent. Neutralizing anti-IL-6 antibodies inhibited IL-6 activity in FRLB cultures but did not affect bone resorption, even in the IL-1 stimulated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Bertolini
D R
DR
Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA.
Votta
B
B
Hoffman
S
S
Strassmann
G
G
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000494:pharmacology; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical
D007375:Interleukin-1; D015850:Interleukin-6; D010281:Parathyroid Hormone; D002117:Calcitriol; D015232:Dinoprostone