Significant elevation of serum interleukin-18 levels in patients with acute pancreatitis.
BACKGROUND
We have reported that peripheral lymphocyte reduction due to apoptosis is linked to the development of subsequent infectious complications in patients with severe acute pancreatitis and that Th1 (helper T cell type 1)/Th2 (helper T cell type 2) balance tends to cause Th1 suppression in experimental severe acute pancreatitis. It has been reported that interleukin (IL)-18 is a cytokine produced from Kupffer cells and activated macrophages, and that IL-18 acts on Th1 cells and in combination with IL-12 strongly induces production of interferon-gamma. However, the role of IL-18 in acute pancreatitis has not yet been fully understood.


METHODS
Serum IL-18 concentrations were determined by an enzyme-linked immunosorbent assay in 43 patients with acute pancreatitis at the time of admission. The relationships with etiology, pancreatic necrosis, severity, blood biochemical parameters on admission, infection, and organ dysfunction during the clinical course and prognosis were analyzed.


RESULTS
Serum IL-18 levels in patients with acute pancreatitis (656+/- 11pg/ml) were significantly higher than those in healthy volunteers (126+/- pg/ml). Serum IL-18 levels were significantly positively correlated with the Ranson score and Japanese severity score. Among the blood biochemical parameters on admission, base excess and total protein were significantly negatively correlated with serum IL-18 levels. Moreover, the CD4/CD8 rate of lymphocytes, serum IL-6 levels, and serum IL-8 levels were significantly positively correlated with serum IL-18 levels. On day 7 after admission, the CD4/CD8 rate of lymphocytes and the rate of CD4-positive lymphocytes were significantly positively correlated with serum IL-18 levels. Furthermore, serum IL-18 levels in patients with hepatic dysfunction (980+/- 25pg/ml) were significantly higher than those without hepatic dysfunction (464+/- 8pg/ml). Serum IL-18 levels were not related to infection or prognosis. Elevation of serum IL-18 levels continued during 4 weeks after admission.


CONCLUSIONS
These results suggest that serum IL-18 levels are significantly elevated and are correlated with severity in patients with acute pancreatitis and that IL-18 may be closely related to helper T cell response and hepatic dysfunction in this disease.
Department of Gastroenterological Surgery, Kobe University Graduate School of Medical Sciences, Kobe 650-0017, Japan.
Takashi
T
Ueda
Yoshifumi
Y
Takeyama
Takeo
T
Yasuda
Naoki
N
Matsumura
Hidehiro
H
Sawa
Takahiro
T
Nakajima
Tetsuo
T
Ajiki
Yasuhiro
Y
Fujino
Yasuyuki
Y
Suzuki
Yoshikazu
Y
Kuroda
D000208:Acute Disease; D001798:Blood Proteins / Q000032:analysis; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020382:Interleukin-18 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000097:blood*; D012720:Severity of Illness Index; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D001798:Blood Proteins; D020382:Interleukin-18; D015850:Interleukin-6; D016209:Interleukin-8