246 LABILE IRON POOL (LIP) ASSOCIATED TO ACTIVATED MACROPHAGES PLAYS A CENTRAL ROLE IN IRON MEDIATED TOXICITY IN ACLF WITH MULTI-ORGAN FAILURE

Autor: H.C. Harsha, Chandan Kumar, D.K. Kumar, N.T. Pati, Jaswinder Singh Maras, Shiv Kumar Sarin, Anima Pandey
Rok vydání: 2012
Předmět:
Zdroj: Journal of Hepatology. 56:S103
ISSN: 0168-8278
Popis: responses to endotoxin and bacterial challenge at baseline, and following 2-hour stimulation with lipopolysaccharide (LPS) and ammonia. Proand anti-inflammatory cytokines were determined by CBA. Results: Baseline neutrophil TLR9 expression was significantly higher in patients with HE (ALF: Grade 3/4 versus controls: p< 0.02, versus grade 0–2: p < 0.03) (Cirrhotics: Grade 3/4 versus controls: p < 0.03, versus grade 0–2: p < 0.05). Moreover their baseline TLR9 expression was associated with severity of HE and higher IL6 and IL8 levels. CD16 expression downregulated by a median of 45% (range 25–85%) in ALF patients with grade 3/4 HE compared to controls and in cirrhotics by a median of 88% (range 5–90%) (Grade 3/4 versus controls: p < 0.05). Baseline CD11b expression did not differ between controls and patients. Exposure to LPS and ammonia upregulated TLR9 and CD11b and downregulated CD16. Conclusion: Neutrophil TLR9 expression in patients with ALF and cirrhosis serves as a useful biomarker that differentiates those who develop high grade HE from those who do not. High baseline TLR9 expression and low CD16 expression promote a pro-inflammatory cytokine milieu that may help to explain the propensity to develop infection and why inflammation hastens the development of HE. TLR9 antagonists may be of therapeutic value in restoring neutrophil activity.
Databáze: OpenAIRE