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Hydroxychloroquine inhibits matrix metalloprotease activity in experimental calcium pyrophosphate dihydrate (CPPD) crystal induced inflammation in the rat subcutaneous air pouch

Abstract

Subacute and chronic CPPD crystal induced inflammation can be difficult to manage. We have used the rat subcutaneous air pouch to study the treatment of experimental CPPD crystal induced inflammation with hydroxychloroquine. The drug was given by gavage at dosages of 10 mg/kg, 40 mg/kg, and 100 mg/kg, and the effect was compared with normal saline. Local leukocyte influx, matrix metalloprotease (MMP), prostaglandin E-2 (PGE2), tumor necrosis factor-α (TNF-α) levels, and biopsies of pouch lining were studied at 6, 24, and 72 h after injection of CPPD crystals into the air pouch. MMP activity was elevated at 6 h after injections with CPPD crystals. MMP levels were significantly lower in hydroxychloroquine treated than in control rats (p < 0.05) at 10 mg/kg and 100 mg/kg of hydroxychloroquine at 72 h. No differences in any other measures of inflammation were noted. The data presented here suggest that clinical studies using hydroxychloroquine in patients with chronic CPPD disease may be warranted.

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Meng, Zh., Baker, D.G., Branigan, P. et al. Hydroxychloroquine inhibits matrix metalloprotease activity in experimental calcium pyrophosphate dihydrate (CPPD) crystal induced inflammation in the rat subcutaneous air pouch. Inflammopharmacology 8, 113–121 (2000). https://doi.org/10.1023/B:INFL.0000041137.92230.64

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  • DOI: https://doi.org/10.1023/B:INFL.0000041137.92230.64