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
Jj. Powell et al., 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, SURGERY, 129(5), 2001, pp. 633-640
Background. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and i
nterleukin-1 beta (IL-1 beta) and their endogenous antagonists such as IL-l
receptor antagonist (IL-1RA) are important mediators of disease severity i
n acute pancreatitis. Because the level of secretion of these cytokines is
determined in part by genetic factors, the aim of this study: was to examin
e the influence of genetically determined cytokine secretion upon disease s
everity in acute pancreatitis.
Methods. TNF (TNF-308, TNFB), IL-1 beta, and IL-1 receptor antagonist (IL-I
RA) 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-1 beta, 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-1 beta, and IL-1RA gene pol
ymorphisms were similar in patients with mild or severe acute pancreatitis.
Further, no difference in gene polymorphism frequencies was observed betwe
en patients with acute pancreatitis and healthy controls. With respect to p
henotype, the secretion of TNF-alpha was similar in patients with previous
mild and severe acute pancreatitis; however, the IL-1 beta: IL-1RA ratio wa
s significantly lower in patients with previous severe acute pancreatitis t
han in those with mild disease.
Conclusions. Our observations suggest that genetic factors are not importan
t in determining TNF-alpha secretion in patients with acute pancreatitis. H
owever; a predetermined imbalance between IL-1 beta and its antagonist IL-1
RA would appear to exist in patients with severe acute pancreatitis, althou
gh the genetic basis for this altered relationship could not be determined.