Interleukin-4 inhibits bone resorption through an effect on osteoclasts and proinflammatory cytokines in an ex vivo model of bone resorption in rheumatoid arthritis.
OBJECTIVE
To assess local bone resorption in the context of rheumatoid synovitis and its modulation by interleukin-4 (IL-4).


METHODS
We developed an ex vivo model of bone resorption using juxtaarticular samples of bone obtained during joint surgery. We studied the histomorphometric parameters of bone resorption and the regulation of the production of IL-6, leukemia inhibitory factor (LIF), and the collagen cross-link pyridinoline, which is released during bone resorption in vivo.


RESULTS
This was a sensitive and dynamic model of bone resorption. The bone samples produced high levels of pyridinoline and as much cytokine as synovium pieces obtained from the same joint. IL-4 induced a 70% reduction of IL-6 and LIF production by bone pieces and reduced pyridinoline levels. Histomorphometric studies performed on bone samples indicated a 35% increase in the mean total bone area after 7 days of treatment with IL-4. More importantly, with IL-4, osteoclasts were not detectable in the bone sections.


CONCLUSIONS
The inhibitory effect of IL-4 on bone resorption extends our knowledge of its antiinflammatory properties and suggests that the inflammatory cytokine imbalance in rheumatoid synovium also contributes to defects in bone resorption in RA.
Miossec
P
P
Department of Immunology, Hôpital Edouard Herriot, Lyon, France.
Chomarat
P
P
Dechanet
J
J
Moreau
J F
JF
Roux
J P
JP
Delmas
P
P
Banchereau
J
J
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000503:physiopathology*; D001862:Bone Resorption / Q000517:prevention & control*; D001842:Bone and Bones / Q000378:metabolism; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D007596:Joints / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects*
D003432:Cross-Linking Reagents; D016207:Cytokines; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D015847:Interleukin-4; D003094:Collagen