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Signalling Profiles of Blood Leucocytes in Sepsis and in Acute Pancreatitis in Relation to Disease Severity
Author(s) -
Kuuliala K.,
Penttilä A. K.,
Kaukonen K.M.,
Mustonen H.,
Kuuliala A.,
Oiva J.,
Hämäläinen M.,
Moilanen E.,
Pettilä V.,
Puolakkainen P.,
Kylänpää L.,
Repo H.
Publication year - 2018
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12630
Subject(s) - sepsis , acute pancreatitis , medicine , phosphorylation , pancreatitis , septic shock , monocyte , intracellular , interleukin 6 , immunology , flow cytometry , tumor necrosis factor alpha , stat , kinase , cytokine , endocrinology , biology , stat3 , biochemistry , microbiology and biotechnology
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 ( STAT s) 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), pSTAT 1 levels of monocytes promoted by IL ‐6 were lower ( P < 0.05 for all), and STAT 3 was constitutively phosphorylated in monocytes, neutrophils and lymphocytes ( P < 0.001 for all). In AP , severity was associated with proportions of pSTAT 1‐positive monocytes and lymphocytes promoted by IL ‐6 ( P < 0.01 for both), constitutive STAT 3 phosphorylation in neutrophils ( P < 0.05), but not with any of the pNF ‐ ĸB levels. Monocyte pSTAT 3 fluorescence intensity, promoted by IL ‐6, was lower in sepsis and AP patients with OD than in AP patients without OD ( P < 0.001). Collectively, signalling aberrations in sepsis with OD mimic those described previously in AP with OD . Possibility that aberrations in STAT 1 and STAT 3 pathways provide novel markers predicting evolution of OD warrants studies including patients presenting without OD but developing it during follow‐up.