Inhibition of the inflammasome is a component of immunoparalysis in Gram-negative sepsis
Abstract number: O79
Giamarellos-Bourboulis E.J., van de Veerdonk F.L., Mouktaroudi M., Raftogiannis M., Antonopoulou A., Georgitsi M., van der Meer J., Netea M.G.
Objective: Immunoparalysis in sepsis is characterized by impairment of cytokine production by monocytes. Interleukin (IL)-1b to be produced requires cleavage of its pro-form that is mediated through the inflammasome. The function of inflammasome in sepsis was assessed.
Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 34 healthy volunteers and from 92 patients with sepsis (49 uncomplicated sepsis; 26 severe sepsis; and 16 with septic shock defined by ACCP/SCCM 1992 criteria) caused by Gram-negative bacteria. PBMCs were stimulated with a variety of stimuli in the absence and presence of caspase-1 inhibitor and of crystals of monosodium urate (MSU) that is an agonist of NALP3 inflammasome. IL-1b was estimated by an enzyme immunoassay. Gene transcripts of IL-1b were estimated by RT-PCR.
Results: Release of IL-1b from PBMCs of septic patients was significantly reduced after stimulation with LPS and heat-inactivated isolates (Figure 1a, asterisks denote significant differences with controls). Gene transcripts of IL-1b were lower compared with healthy controls but this difference was not significant. Effect of caspase-1 inhibitor on release of IL-1b is shown in Figure 1b (asterisk denotes significant differences in the absence of inhibitor). Stimulation with MSU yielded significant releases of IL-1b from PBMCs of healthy controls but not of patients with sepsis (Figure 1c). LPS and MSU acted in synergy for the production of IL-1b by PBMCs of healthy volunteers but not of patients with sepsis (Figure 1d; asterisk denotes significant difference by the LPS and MSU compared with single LPS).
Conclusions: Inhibition of the inflammasome is a considerable component of the phenomenon of immunoparalysis presented among patients with Gram-negative sepsis.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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