The type II decoy receptor of IL-1 inhibits murine collagen-induced arthritis.
IL-1 is a key cytokine involved in the inflammatory response. The type II receptor of IL-1 (IL-1RII) acts as a decoy receptor, binding and inhibiting the effect of IL-1. This study was undertaken to establish whether IL-1RII can ameliorate collagen-induced arthritis, a model of inflammatory arthritis in mice. We used human keratinocytes transfected with the human (h)IL-1 RII gene as a source of hIL-1 RII protein. We showed that these cells expressed both the membrane and soluble form of receptor. In vitro, IL-1-stimulated murine macrophage cells showed a decreased expression of TNF-alpha in the presence of hIL-1 RII. We engrafted the hIL-1RII-transfected cells in the back of mice developing collagen-induced arthritis. We found that clinical and histological parameters of arthritis were significantly decreased in mice treated with cells producing hIL-1RII. In addition, hIL-1RII administration was able to reduce the expression of mRNA for IL-6 and myeloperoxidase in the joints of treated animals. These data show that hIL-1 RII anti-inflammatory properties in the model of collagen-induced arthritis in mice and could have a regulatory role in rheumatoid arthritis.
Bessis
N
N
UPRES EA-2361, UFR Léonard de Vinci, Université Paris-Nord, Bobigny, France.
Guéry
L
L
Mantovani
A
A
Vecchi
A
A
Sims
J E
JE
Fradelizi
D
D
Boissier
M C
MC
D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D001483:Base Sequence; D002460:Cell Line; D003094:Collagen / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009195:Peroxidase / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D017931:DNA Primers; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D009195:Peroxidase