Soluble CD14 receptor expression and monocyte heterogeneity but not the C-260T CD14 genotype are associated with severe acute pancreatitis.
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.


METHODS
Prospective case-matched study.


METHODS
Tertiary pancreatic treatment unit in the United Kingdom.


METHODS
Patients with pancreatitis and controls.


METHODS
DNA from 117 patients with pancreatitis (34 severe) and 263 controls underwent CD14 genotyping using restriction fragment length polymorphism-polymerase chain reaction.


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.
Rahman
Sakhawat H
SH
Academic Unit of Surgery, University of Leeds, General Infirmary, Leeds, West Yorkshire, UK.
Salter
Gwyneth
G
Holmfield
John H M
JH
Larvin
Michael
M
McMahon
Michael J
MJ
D000208:Acute Disease; D001483:Base Sequence; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009000:Monocytes; D009102:Multiple Organ Failure / Q000401:mortality; D010195:Pancreatitis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018570:Risk Assessment; D012720:Severity of Illness Index; D012995:Solubility; D018709:Statistics, Nonparametric; D015996:Survival Rate
D005819:Genetic Markers; D018950:Lipopolysaccharide Receptors