Effect of pathogenic crystals on the production of pro- and anti-inflammatory cytokines by different leukocyte populations

PURPOSE: To evaluate cytokine production in vitro by different types of leukocytes stimulated with monosodium urate (MSU), calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals.MATERIAL AND METHODS: Polymorphonuclear cells (PMN), monocytes and lymphocytes, isolated from healthy volunteer blood, were stimulated for different time periods with increasing MSU, CPP or BCP crystal concentrations. IL-1beta, IL-8, IL-6, CCL2, IL-1Ra and TGFbeta1 were determined by ELISA.RESULTS: Exposure of PMN to different crystals resulted in a moderate IL-8 and IL-1Ra release. Stimulation of monocytes induced a significant production of all the cytokines evaluated. The highest levels of IL-1beta, IL-6, CCL2 and IL-8 were observed with MSU at 0.5mg/ml, CPP at 0.01-0.05mg/ml and BCP at 1mg/ml after 18-48h and then decreased. At the same crystal concentrations, IL-1Ra and TGFbeta1 increased until the end of the experiment. Treatment of lymphocytes with different crystals did not induce cytokine release.CONCLUSION: This study demonstrates that PMN, monocytes and lymphocytes from the same donor respond differently after stimulation with MSU, CPP or BCP crystals, depending on the dose and the time of exposure. Crystals induce a rapid increase of pro-inflammatory cytokines, whereas longer time is required to release high levels of anti-inflammatory cytokines.