Differential effects of colchicine in blood mononuclear cells of patients with Behçet disease in relation to colchicine responsiveness

Abstract

BACKGROUND: Colchicine, a first-line drug for the treatment of Behçet disease (BD), inhibits caspase-1 activation and inflammatory cytokine production. However, therapeutic and preventive effects are not observed in some patients with BD.

OBJECTIVE: To explore whether the effects of colchicine on proinflammatory cytokine expression and cell death in peripheral blood mononuclear cells (PBMCs) from patients with BD are associated with responsiveness to colchicine.

METHODS: Activation of caspase-1, transcription and secretion of interleukin (IL)-1β, tumour necrosis factor (TNF)-α and IL-6, and release of lactate dehydrogenase (LDH) in PBMCs isolated from healthy controls and patients with BD were analysed in the presence or absence of colchicine and upon stimulation with lipopolysaccharide (LPS) plus a caspase-1 activator.

RESULTS: Colchicine significantly modulated monosodium urate-induced IL-1β release, LPS-stimulated LDH release, and basal transcript levels of TNF-α and IL-6 in healthy controls and BD colchicine responders, but not in BD colchicine nonresponders. Notably, colchicine showed contrasting effects on LPS-stimulated IL-1β transcription, i.e. it increased in responders but decreased in nonresponders. Also, higher levels of TNF-α and IL-6 transcripts were observed in LPS-stimulated PBMCs from nonresponders compared with responders.

CONCLUSIONS: This study shows different effects of colchicine on PBMCs from patients with BD according to their responsiveness to colchicine. Predicting responsiveness to colchicine in patients with BD may, therefore, be possible by examining alterations in IL-1β transcript levels in LPS-stimulated PBMCs after colchicine treatment.