Potential role of interleukin-18 in liver disease associated with insulin resistance.
OBJECTIVE
Interleukin (IL)-18 has been associated with obesity and insulin resistance, both risk factors for the development of liver disease, but the role of IL-18 in liver disease associated with insulin resistance is presently unknown. We hypothesized that circulating IL-18 would be related to serum concentrations of liver chemistry tests (LCTs) in apparently healthy subjects and wished to study whether this correlation was dependent on insulin sensitivity (S(I)).


METHODS
One hundred six apparently healthy white men consecutively enrolled in a cross-sectional, population-based study dealing with S(I) in men were studied, and S(I) (minimal model analysis), LCTs (colorimetry), and IL-18 serum concentrations (immunoassay) were assessed.


RESULTS
Compared with subjects in the lowest quartile for serum IL-18, subjects in the highest quartile exhibited increased serum triglycerides and decreased S(I), in addition to higher serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (all p < 0.05). The direct association between both ALT and AST and IL-18 was further confirmed by examining the distribution of serum IL-18 by quartiles of ALT and AST. Subjects in the highest quartile for serum ALT and AST had higher IL-18 concentrations compared with subjects in the lowest quartile for these LCTs (both p = 0.01). In multiple regression analysis, IL-18, but not S(I), was an independent predictor of serum concentrations of ALT and AST, explaining 7% and 4% of their variance, respectively.


CONCLUSIONS
In summary, IL-18 serum concentrations are associated in apparently healthy humans with plasma concentrations of various LCTs. IL-18 could contribute to the development of liver disease associated with insulin resistance.
López-Bermejo
Abel
A
Unit of Diabetes, Endocrinology, and Nutrition, Dr. Josep Trueta Hospital, Av. Francia s/n, 17007 Girona, Spain. uden.alopez@htrueta.scs.es
Bosch
Montserrat
M
Recasens
Mònica
M
Biarnés
Josefina
J
Esteve
Eduardo
E
Casamitjana
Roser
R
Vendrell
Joan
J
Ricart
Wifredo
W
Fernández-Real
José-Manuel
JM
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000032:analysis / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D020382:Interleukin-18 / Q000097:blood*; D008099:Liver / Q000201:enzymology; D008107:Liver Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D020382:Interleukin-18; D014280:Triglycerides; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase