Ascites from patients with alcoholic liver cirrhosis contains higher IGF-I bioactivity than serum.
OBJECTIVE
Patients with liver cirrhosis have diminished hepatic IGF-I generation, resulting in low circulating levels, whereas data on IGF-I in ascites are sparse. Therefore, we compared the IGF-system in serum and ascites from cirrhotic patients.


METHODS
The study comprised 43 patients (12 females) with ascites and liver function of 58 +/- 10% of normal. Serum and ascites were collected concomitantly in the fasting state. In 11 patients, second serum and ascitic samples were collected within the first week. Eleven matched controls were also included. All samples were assayed for IGF-related parameters by immunoassays and by cell-based IGF-I bioassay.


RESULTS
As compared with controls, serum total IGF-I, total IGF-II, pro-IGF-II and bioactive IGF-I were reduced in liver patients, whereas IGF-binding protein 1 (IGFBP-1), IGFBP-2 and the soluble IGF-II receptor were elevated (P < 0.005 for all). In ascites, all IGF-related peptides but pro-IGF-II were further reduced as compared with serum (P < 0.001). By contrast, bioactive IGF-I was fourfold elevated in ascites as compared with serum (2.20 +/- 0.33 vs. 0.55 +/- 0.08 microg/l, P < 0.001). In ascites, the IGF-I bioactivity signal was completely blocked by addition of IGFBP-3. Repetitive measurements (n = 11) in ascites showed that all peptides but IGFBP-1 remained unchanged within 1 week.


CONCLUSIONS
It is a novel observation that the in vitro bioactivity of IGF-I can be higher in fluids from an extravascular compartment than in serum, in contrast to immunoreactive levels. This supports different roles for endocrine and paracrine/autocrine IGF-I, but the pathophysiological significance of our observation remains to be clarified.
Jeyaratnaganthan
Nilani
N
The Medical Research Laboratories, Clinical Institute, and Medical Department M (Diabetes & Endocrinology), Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
Grønbaek
Henning
H
Holland-Fischer
Peter
P
Espelund
Ulrick
U
Chen
Jian-Wen
JW
Flyvbjerg
Allan
A
Vilstrup
Hendrik
H
Frystyk
Jan
J
D001201:Ascites / Q000097:blood / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D016014:Linear Models; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II