Effects of soluble interleukin-1 type II receptor on rabbit antigen-induced arthritis: clinical, biochemical and histological assessment.
OBJECTIVE
To investigate the effects of soluble interleukin-1 (IL-1) type II receptor (sIL-1RII) on a number of clinical, biochemical and histological parameters in rabbit antigen-induced arthritis.


METHODS
Arthritis was induced by intra-articular injection of methylated bovine serum albumin (mBSA) into rabbits pre-sensitized to the same antigen. An initial i.v. bolus of sIL-1RII was administered, followed by s.c. mini-pump dosing for 14 days, starting at the time of the arthritis induction. Animals received vehicle (saline 500 microl + 5 microl/h), low-dose sIL-1RII (13.4 microg + 1.34 microg/h) or high-dose sIL-1RII (40.2 microg + 4.02 microg/h).


RESULTS
Marked, dose-related inhibition of joint diameter, plasma prostaglandin E2 (PGE2), and synovial fluid IL-1alpha and IL-1beta concentrations were seen after administration of sIL-1RII. However, synovial fluid PGE2 concentrations and synovial fluid cell counts were not affected. A significant inhibitory effect was also seen histologically on soft-tissue swelling and joint damage with high-dose sIL-1RII.


CONCLUSIONS
These results demonstrate that IL-1 plays an important role in the pathogenesis of rabbit antigen-induced arthritis, thus confirming it as an excellent animal model with respect to evaluating anti-cytokine therapies for rheumatoid arthritis.
Dawson
J
J
Department of Arthritis and Bone Metabolism, Novartis Pharma AG, Basel, Switzerland.
Engelhardt
P
P
Kastelic
T
T
Cheneval
D
D
MacKenzie
A
A
Ramage
P
P
D000818:Animals; D018501:Antirheumatic Agents / Q000032:analysis / Q000276:immunology; D016918:Arthritis, Reactive / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D015232:Dinoprostone / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D005260:Female; D006965:Hyperplasia; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000032:analysis / Q000276:immunology; D007719:Knee Joint / Q000473:pathology; D011817:Rabbits; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D053574:Receptors, Interleukin-1 Type II; D012710:Serum Albumin, Bovine; D012795:Sialoglycoproteins / Q000032:analysis / Q000276:immunology; D012995:Solubility; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D012710:Serum Albumin, Bovine; D015232:Dinoprostone