Interleukin-4 cellular gene therapy and osteoprotegerin decrease inflammation-associated bone resorption in collagen-induced arthritis.
To evaluate the respective action of IL-4, an anti-inflammatory cytokine, and OPG, an inhibitor of bone resorption, on the inflammatory process and the associated bone resorption in collagen-induced arthritis (CIA). After CIA induction, DBA/1 mice were treated with OPG or with IL-4 DBA/1 transfected fibroblasts or both OPG + IL-4. CIA significantly improved in IL-4 groups. OPG had no effect on arthritis clinical scores but histologic scores were reduced in OPG, IL-4, and OPG + IL-4 groups vs. nontreated CIA mice. OPG increased significantly BMD and decreased by 45% D-pyridinolin levels. Moreover association of IL-4 and OPG exerted an additive effect of BMD and resorption marker (-68%). Production of IFN-gamma in the supernatants of spleen cells was reduced in IL-4 treated mice. OPG had a moderate effect on IFN-gamma, but potentiated the inhibitory effect of IL-4. OPG and IL-4 prevent bone loss in CIA-mice model and could have additive effects on IFN-gamma secretion.
Saidenberg-Kermanac'h
Nathalie
N
UPRES EA-3408 and Department of Rheumatology, Avicenne Hospital (AP-HP), Bobigny Medical School, Paris 13 University, France.
Bessis
Natacha
N
Lemeiter
Delphine
D
de Vernejoul
Marie-Christine
MC
Boissier
Marie-Christophe
MC
Cohen-Solal
Martine
M
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005347:Fibroblasts / Q000166:cytology; D015316:Genetic Therapy / Q000379:methods*; D006023:Glycoproteins / Q000008:administration & dosage* / Q000627:therapeutic use; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000008:administration & dosage* / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor; D014162:Transfection
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse; D015847:Interleukin-4; D007371:Interferon-gamma; D003094:Collagen