Document Detail


Soluble CD14 receptor expression and monocyte heterogeneity but not the C-260T CD14 genotype are associated with severe acute pancreatitis.
MedLine Citation:
PMID:  15599151     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Soluble CD14 is derived from a membrane glycoprotein, and it enhances endothelial cytokine responses to lipopolysaccharide. We studied the role of soluble CD14 in the pathogenesis of the systemic inflammatory response associated with acute pancreatitis, to determine whether altered expression was due to a functional C-260T polymorphism in the CD14 promoter gene or altered monocyte heterogeneity. DESIGN: Prospective case-matched study. SETTING: Tertiary pancreatic treatment unit in the United Kingdom. SUBJECTS: Patients with pancreatitis and controls. INTERVENTIONS: DNA from 117 patients with pancreatitis (34 severe) and 263 controls underwent CD14 genotyping using restriction fragment length polymorphism-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Peripheral venous blood samples at 24 and 72 hrs after the onset of abdominal pain were analyzed for sCD14 levels. Isolated peripheral blood mononuclear cells were phenotyped for CD14/CD16 receptor expression using immunofluorescence flow cytometry. Disease severity was assessed using Atlanta criteria, Acute Physiology Scores, and C-reactive protein.Soluble CD14 levels were higher in severe (24-hr median, 66.6 ng/mL; 72-hr median, 72.2 ng/mL) compared with mild attacks (24-hr median, 50.7 ng/mL; 72-hr median, 49.7 ng/mL, p < .001), although the latter was similar to controls (median, 51 ng/mL). Furthermore, soluble CD14 levels correlated with Acute Physiology Scores (p < .001) and C-reactive protein (p = .01).Peripheral blood mononuclear cells CD14++ (p = .008), CD14+/16+ (p = .003), and CD16++ (p = .015) receptor densities were all increased in severe attacks at 24 hrs. Early CD14+/16+ receptor density correlated with sCD14 (p < .001), Acute Physiology Scores (p < .001), and C-reactive protein (p = 0.006). The CD14 genotype prevalence in acute pancreatitis was similar to controls and failed to correlate with any variables studied. CONCLUSIONS: Increased soluble CD14 expression is associated with the systemic inflammatory response to acute pancreatitis and an expansion of the proinflammatory CD14+/CD16+ monocyte subset. Its targeted disruption may afford some benefit in preventing the development of systemic complications.
Authors:
Sakhawat H Rahman; Gwyneth Salter; John H M Holmfield; Michael Larvin; Michael J McMahon
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Critical care medicine     Volume:  32     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-12-15     Completed Date:  2005-01-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2457-63     Citation Subset:  AIM; IM    
Affiliation:
Academic Unit of Surgery, University of Leeds, General Infirmary, Leeds, West Yorkshire, UK.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Antigens, CD14 / genetics,  metabolism*
Base Sequence
Case-Control Studies
Chi-Square Distribution
Disease Progression
Female
Gene Expression Regulation
Genetic Markers
Genotype
Humans
Male
Molecular Sequence Data
Monocytes
Multiple Organ Failure / mortality
Pancreatitis / genetics*,  mortality,  therapy
Polymorphism, Genetic*
Probability
Prognosis
Prospective Studies
Reference Values
Reverse Transcriptase Polymerase Chain Reaction / methods
Risk Assessment
Severity of Illness Index
Solubility
Statistics, Nonparametric
Survival Rate
Chemical
Reg. No./Substance:
0/Antigens, CD14; 0/Genetic Markers

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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