Colchicine Inhibits Chemokine Production in Monosodium Urate–Stimulated Innate Immune Cells
Laura M. Merlo Pich, Titus Schlüter, Andrei Sarlea, Mihai G. Netea, Calin Popa, Leo A. B. JoostenObjective
Colchicine is a well‐established, widely available drug used to treat inflammatory diseases driven by the innate immune system, most notably gout. Although much research has focused on neutrophils, the first responders in a gout flare, monocytes and lymphocytes, also play critical roles in sustaining the inflammatory response. However, the impact of colchicine on these cell types remains poorly understood. The objective of this study was to assess the in vitro effects of colchicine on primary peripheral blood mononuclear cells (PBMCs) stimulated with monosodium urate (MSU) crystals.
Methods
PBMCs or monocytes from healthy volunteers were isolated and cultured with a one‐hour preincubation of colchicine, followed by a 24‐hour stimulation with MSU crystals and lipopolysaccharide. Supernatants were collected for cytokine quantification and chemotaxis assay, whereas cells were processed for RNA isolation, metabolic analysis, reactive oxygen species (ROS) activity, and phagocytosis.
Results
Colchicine reduced the secretion of several chemokines, notably MCP‐1, whereas no inhibitory effect on the release of proinflammatory cytokines such as interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor (TNF) was observed. Colchicine also reduced MCP‐1 and TNF, but not IL‐1β and IL‐6, production in monocytes. Both MCP‐1 messenger RNA expression and intracellular protein concentrations were inhibited by colchicine, suggesting an effect at transcriptional level. Lower chemokine production is responsible for reduced chemoattraction of monocytes. Moreover, colchicine attenuated ROS production and phagocytic activity in monocytes, alongside suppressing glycolytic metabolism and oxidative phosphorylation.
Conclusion
Colchicine's anti‐inflammatory mechanisms in monocytes and PBMCs consist mainly of reduction of chemokine production and chemoattraction accompanied by changes in cellular metabolism and attenuated ROS production.