tailieunhanh - Báo cáo y học: " Inhibition of caspase-1 activation in gram-negative sepsis and experimental endotoxemia"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Inhibition of caspase-1 activation in gram-negative sepsis and experimental endotoxemia. | Giamarellos-Bourboulis et al. Critical Care 2011 15 R27 http content 15 1 R27 KS CRITICAL CARE RESEARCH Open Access Inhibition of caspase-1 activation in gram-negative sepsis and experimental endotoxemia 12 2 12 1 Evangelos J Giamarellos-Bourboulis 1 Frank L van de Veerdonk Maria Mouktaroudi 1 Maria Raftogiannis Anastasia Antonopoulou1 Leo AB Joosten2 Peter Pickkers3 Athina Savva1 Marianna Georgitsi1 Jos WM van der Meer2 Mihai G Netea2 Abstract Introduction Down-regulation of ex-vivo cytokine production is a specific feature in patients with sepsis. Cytokine downregulation was studied focusing on caspase-1 activation and conversion of pro-interleukin-13 into interleukin-13 IL-13 . Methods Peripheral blood mononuclear cells were isolated from a 92 patients with sepsis mainly of Gramnegative etiology b 34 healthy volunteers and c 5 healthy individuals enrolled in an experimental endotoxemia study. Cytokine stimulation was assessed in vitro after stimulation with a variety of microbial stimuli. Results Inhibition of IL-13 in sepsis was more profound than tumour necrosis factor TNF . Down-regulation of IL-13 response could not be entirely explained by the moderate inhibition of transcription. We investigated inflammasome activation and found that in patients with sepsis both pro-caspase-1 and activated caspase-1 were markedly decreased. Blocking caspase-1 inhibited the release of IL-13 in healthy volunteers an effect that was lost in septic patients. Finally urate crystals which specifically induce the NLPR3 inflammasome activation induced significant IL-13 production in healthy controls but not in patients with sepsis. These findings were complemented by inhibition of caspase-1 autocleavage as early as two hours after lipopolysaccharide exposure in volunteers. Conclusions These data demonstrate that the inhibition of caspase-1 and defective IL-1 3 production is an important immunological feature in sepsis. Introduction Despite the increase of our knowledge