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Diferentes param. en pacien. k no responden a la colchicina

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Differential effects of colchicine in blood mononuclear cells of Behcet’s disease in relation to colchicine responsiveness

Colchicine, a first line drug for treatment of Behcet’s disease (BD), inhibits caspase-1 activation and inflammatory cytokine production. However, therapeutic and preventive effects are not observed in some patients with BD. To explore whether the effects of colchicine on proinflammatory cytokine expression and cell death in peripheral blood mononuclear cells (PBMCs) from BD patients are associated with colchicine responsiveness. Activation of caspase-1, transcription and secretion of IL-1β, TNFα and IL-6, and release of lactate dehydrogenase (LDH) in PBMCs isolated from healthy controls and BD patients were analysed in the presence and absence of colchicine and upon stimulation with lipopolysaccharide (LPS) plus a caspase-1 activator. Colchicine significantly modulated monosodium urate-induced IL-1β release, LPS-stimulated LDH release, and basal transcript levels of TNFα and IL-6 in healthy controls and BD colchicine responders, but not in BD colchicine non-responders. Notably, colchicine showed contrasting effects on LPS-stimulated IL-1β transcription, i.e., it increased in responders but decreased in non-responders. Also, higher levels of TNFα and IL-6 transcripts were observed in LPS-stimulated PBMCs from non-responders compared with responders. This study shows different effects of colchicine on PBMCs from BD patients according to colchicine responsiveness. Predicting colchicine responsiveness in BD patients may, therefore, be possible by examining alterations in IL-1β transcript levels in LPS-stimulated PBMCs after colchicine treatment.
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