Abstract
Background. Cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) 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-1β, 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-α,
IL-1β, 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-1β, 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-α was similar in
patients with previous mild and severe acute pancreatitis; however, the IL-1β: 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-α
secretion in patients with acute pancreatitis. However, a predetermined imbalance
between IL-1β 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. (Surgery 2001;129:633-40.)
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Article info
Publication history
Accepted:
December 5,
2000
Footnotes
*Reprint requests: A. K. Siriwardena, MD, FRCS, Department of Surgery, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, United Kingdom.
**Surgery 2001;129:633-40.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
