Evidence against a role for polymorphisms at tumor necrosis factor, interleukin-1 and interleukin-1 receptor antagonist gene loci in the regulation of disease severity in acute pancreatitis.
BACKGROUND
Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and their endogenous antagonists such as IL-1 receptor antagonist (IL-1RA) are important mediators of disease severity in acute pancreatitis. Because the level of secretion of these cytokines is determined in part by genetic factors, the aim of this study was to examine the influence of genetically determined cytokine secretion upon disease severity in acute pancreatitis.


METHODS
TNF (TNF-308, TNFB), IL-1beta, and IL-1 receptor antagonist (IL-1RA) genotypes were determined for 190 patients with acute pancreatitis and 102 healthy volunteers. To further assess the influence of genetic factors, the cytokine phenotype for TNF-alpha, IL-1beta, and IL-1RA was determined by using a whole blood culture technique in 51 patients after recovery.


RESULTS
The distributions of TNF-308, TNFB, IL-1beta, and IL-1RA gene polymorphisms were similar in patients with mild or severe acute pancreatitis. Further, no difference in gene polymorphism frequencies was observed between patients with acute pancreatitis and healthy controls. With respect to phenotype, the secretion of TNF-alpha was similar in patients with previous mild and severe acute pancreatitis; however, the IL-1beta: IL-1RA ratio was significantly lower in patients with previous severe acute pancreatitis than in those with mild disease.


CONCLUSIONS
Our observations suggest that genetic factors are not important in determining TNF-alpha secretion in patients with acute pancreatitis. However, a predetermined imbalance between IL-1beta and its antagonist IL-1RA would appear to exist in patients with severe acute pancreatitis, although the genetic basis for this altered relationship could not be determined.
Powell
J J
JJ
University Department of Surgical and Clinical Sciences, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
Fearon
K C
KC
Siriwardena
A K
AK
Ross
J A
JA
D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000235:genetics* / Q000276:immunology*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D012795:Sialoglycoproteins / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha