Counter-regulatory effects of procalcitonin and indoxyl sulphate on net albumin secretion by cultured rat hepatocytes.
BACKGROUND
Although hypoalbuminaemia is a significant predictor of mortality in haemodialysis (HD) patients, the pathophysiological mechanisms involved remain to be determined. Albumin is a negative acute-phase reactant and many proinflammatory substances are elevated in HD patients. We investigated factors that may affect liver albumin synthesis.


METHODS
Hepatocytes were isolated from rat livers and were cultured with interleukin (IL)-4, IL-6, IL-12, tumor necrosis factor (TNF)-alpha, procalcitonin (PCT), a sensitive marker of infection, and indoxyl sulphate (IS), a uraemic toxin. Albumin levels in the supernatant were measured by enzyme-linked immunosorbent assay. Albumin mRNA expression was determined by reverse transcriptase polymerase chain reaction.


RESULTS
IL-6 and TNF-alpha significantly decreased albumin levels in a dose-dependent manner (P<0.01 and P<0.05, respectively). In contrast, IL-4 and IL-12 did not modulate albumin production. PCT and IS significantly and dose-dependently increased albumin levels (both P<0.01). PCT increased albumin mRNA expression in the hepatocytes (P = 0.05) and dose-dependently abrogated IL-6-induced suppression of albumin synthesis (P<0.01). IS also blocked the IL-6-induced decrease in net albumin secretion (P<0.01).


CONCLUSIONS
Our findings indicate that PCT and IS protect against suppression of hepatic albumin synthesis caused by proinflammatory cytokines, suggesting their potential role in preventing hypoalbuminaemia in HD patients.
Odamaki
Mari
M
Department of Clinical Nutrition, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka, 422-8526, Japan. odamari@u-shizuoka-ken.ac.jp
Kato
Akihiko
A
Kumagai
Hiromichi
H
Hishida
Akira
A
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D002116:Calcitonin / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D007200:Indican / Q000502:physiology*; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D011498:Protein Precursors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; C000606591:Calca protein, rat; D016207:Cytokines; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D007200:Indican