Abstract
Aim:
To investigate the mechanisms of interleukin-1 receptor antagonist (IL-1ra) in the treatment of adjuvant arthritis (AA).
Methods:
AA was induced in rats by treatment with Freund's complete adjuvant (FCA). Rats were given an intracutaneous injection of IL-1ra (2.5, 10, 40 mg/kg, 3 times per day) from d 14 to d 21 after immunization. Synoviocyte proliferation and the activity of IL-1 were determined by using MTT assay. Tumor necrosis factor alpha (TNF-α) and prostaglandin E2 (PGE2) concentrations were measured by radioimmunoassay. The ultrastructure of synoviocytes was observed by using a transmission electron microscope. Phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulating kinase (ERK) and p38 kinase were detected by Western blot analysis.
Results:
IL-1ra (10 and 40 mg/kg, ic, d 14-21) modulated the secondary inflammatory reaction (P<0.01), ultrastructure of synoviocytes and mitogen-activated protein kinase (MAPK) phosphorylation in AA rats. The administration of IL-1ra (10 and 40 mg/kg, ic, d 14-21) in AA rats significantly decreased the production of IL-1, PGE2 and TNF-α by macrophage-like synoviocytes (MLS) (P<0.01). IL-1ra (2.5 mg/kg) also decreased the production of PGE2 (P<0.01) and TNF-α (P<0.05) by MLS in AA rats. The increased phosphorylation of MAPK and cell proliferation in fibro-blast-like synoviocytes (FLS) stimulated by supernatants of MLS in AA rats was also inhibited by IL-1ra (10 and 40 mg/kg, ic, d 14-21).
Conclusion:
IL-1ra has anti-inflammatory effects because it modulates the ultrastructure of synoviocytes, decreases the production of pro-inflammatory mediators by MLS, and inhibits the phosphorylation of MAPK in FLS.
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Project supported by the National Natural Science Foundation of China (No 30271606, No 30572356), and the Natural Science Foundation of Anhui Province, China (No 050430903, No 00044411).
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Zheng, Yq., Wei, W., Dai, M. et al. Interleukin-1 receptor antagonist intervenes in signaling between different types of synoviocytes in rats with adjuvant arthritis. Acta Pharmacol Sin 27, 111–118 (2006). https://doi.org/10.1111/j.1745-7254.2006.00234.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00234.x
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