科研之友
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摘要
Background Colchicine, a first-line drug for the treatment of Behcet disease (BD), inhibits caspase-1 activation and inflammatory cytokine production. However, therapeutic and preventive effects are not observed in some patients with BD. %26lt;br%26gt;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. %26lt;br%26gt;Methods Activation of caspase-1, transcription and secretion of interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha 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. %26lt;br%26gt;Results Colchicine significantly modulated monosodium urate-induced IL-1 beta release, LPS-stimulated LDH release, and basal transcript levels of TNF-alpha 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-1 beta transcription, i.e. it increased in responders but decreased in nonresponders. Also, higher levels of TNF-alpha and IL-6 transcripts were observed in LPS-stimulated PBMCs from nonresponders compared with responders. %26lt;br%26gt;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-1 alpha transcript levels in LPS-stimulated PBMCs after colchicine treatment.
- 出版日期2012-10
