Signalling Profiles of Blood Leucocytes in Sepsis and in Acute Pancreatitis in Relation to Disease Severity

Abstract Intracellular signalling in blood leucocytes shows multiple aberrations in acute pancreatitis (AP) complicated by organ dysfunction (OD). We studied whether the aberrations associate with severity of AP and occur in sepsis complicated by OD. The study comprises 14 sepsis patients (11 with shock), 18 AP patients (nine mild; six moderately severe; three severe) and 28 healthy volunteers. Within 48 h after admission to hospital, phosphorylation of nuclear factor‐ĸB (NF‐ĸB), signal transducers and activators of transcription (STATs) 1,3, and extracellular signal‐regulated kinases 1/2 were measured from stimulated or non‐stimulated leucocytes using phosphospecific whole blood flow cytometry. In sepsis, as compared with healthy subjects, phosphorylated NF‐ĸB levels of monocytes promoted by bacterial lipopolysaccharides, tumour necrosis factor or Escherichia coli cells were lower (P < 0.001 for all), pSTAT1 levels of monocytes promoted by IL‐6 were lower (P < 0.05 for all), and STAT3 was constitutively phosphorylated in monocytes, neutrophils and lymphocytes (P < 0.001 for all). In AP, severity was associated with proportions of pSTAT1‐positive monocytes and lymphocytes promoted by IL‐6 (P < 0.01 for both), constitutive STAT3 phosphorylation in neutrophils (P < 0.05), but not with any of the pNF‐ĸB levels. Monocyte pSTAT3 fluorescence intensity, promoted by IL‐6, was lower in sepsis and AP patients with OD than in AP patient...
Source: Scandinavian Journal of Immunology - Category: Allergy & Immunology Authors: Tags: Human Immunology Source Type: research