Inhibitory effect of low density lipoprotein on the inflammation-inducing activity of calcium pyrophosphate dihydrate crystals.

OBJECTIVE: It has been proposed that low density lipoprotein (LDL) plays a role in the self-limiting nature of pseudogout inflammation. We investigated changes of LDL concentration in rat air pouch fluid during periods of acute and subsiding inflammation to evaluate whether LDL contributes to inhibiting inflammation of pseudogout. We examined whether LDL binds to calcium pyrophosphate dihydrate (CPPD) crystals as a possible mechanism for reduction of inflammation.

METHODS: In this in vivo study, 5 mg suspensions of CPPD crystals and saline were injected into the rat air pouch. Fluid samples were taken from rat air pouch at 0, 3, 6, 12, 24, and 48 h after injection. White blood cells in the samples were counted; the remaining fluid was centrifuged and concentrations of beta-glucuronidase and PGE2 in the supernatant were measured as inflammatory markers. LDL in the supernatant was immunochemically identified by Western blotting, then pellets containing crystals were examined by the same technique.

RESULTS: LDL was identified in the air pouch 3 h after CPPD crystal injection, and its concentration increased and reached a peak level after 24 h. Inflammatory markers reached maximal level from 6 to 12 h, then decreased after 24 h. In the pellets containing crystals, LDL could not be identified in every specimen.

CONCLUSION: LDL in the rat air pouch increased during the inflammatory course induced by CPPD crystal and the inflammation subsided as the LDL increased. Since some reports indicate LDL was related to reduction of crystal induced inflammation such as gout or pseudogout, we concluded that LDL could contribute to the resolution of acute pseudogout arthritis in vivo with or without binding to CPPD crystals.