Pharmacodynamics of recombinant human interleukin-1 receptor antagonist in treatment of osteoarthritis
Objective To observe the therapeutic effect of recombinant human interleukin-1 receptor antagonist(rhIL-1Ra)on osteoarthritis(OA)induced by sodium iodoacetate(MIA)in rats.Methods Female Wistar rats were divided into normal control group(11 rats)and model group(55 rats)according to the threshold of heat pain.After 3 d of modeling,the model group was randomly divided into solvent control model group(placebo),low-dose group(9 mg/kg rhIL-1Ra)and high-dose group(18 mg/kg rhIL-1Ra),with 12 rats in each group,according to the swelling rate of the left hindlimb knee joint,which were subcutaneously injected through neck,1 mL/kg once a day for 14 consecutive days.The diameter of the left hindlimb knee joint was measured 3 d before and after modeling and 2,4,7 and 14 d after the initial administration,and the swelling degree,swelling rate and swelling inhibition rate were calculated.The knee joint specimens of the left hindlimb were fixed,embedded in paraffin,sectioned,then stained with safranin O,and scored the pathological lesion under microscope.Results After 3 d of modeling,the swelling rates of knee joint of rats in all groups except normal control group reached about 30％.Compared with the solvent control model group,the swelling degree and swelling rate in the low-dose group decreased at both 2 and 4 d(1.52±0.38 and 1.26±0.43)(t=1.924,1.945,each P＜0.05)after adminis-tration,while those in the high-dose group all decreased significantly at 2,4 and 7 d(1.51±0.37,1.15±0.24,and 1.14±0.39)(t=2.976,2.874,2.902,each P＜0.01).Compared with the solvent control model group,the degrees of articular cartilage lesions in the low and high dosage groups(8.33±1.86,8.17±2.79)were similar,and the statistical results of pathological scores showed a slight decrease(t=1.814,each P＞0.05),indicating that the model was estab-lished successfully.Conclusion After 14 d of administration,high dose of rhIL-1Ra significantly reduced the knee joint swelling in acute stage of MIA-induced osteoarthritis in rats,but had no significant effect on the pain perception in MIA-induced chronic knee arthritis,and did not significantly reverse the knee cartilage injury induced by MIA.
Recombinant human interleukin-1 receptor antagonist(rhIL-1Ra)Osteoarthritis(OA)Heat pain thresholdSodium iodoacetate(MIA)
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