Association of serum interleukin-8 levels with the degree of fibrosis in infants with chronic liver disease.
OBJECTIVE
Biliary atresia is a neonatal obstructive cholangiopathy characterized by a destructive, obliterative process affecting both the intrahepatic and extrahepatic ducts of the biliary tree that uniquely presents in the first months of life. The consequence of progressive inflammatory and sclerotic reaction is the development of obstructive jaundice. To determine the proinflammatory cytokine profile in children with biliary atresia, we measured circulating levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and IL-8.


METHODS
Twelve children, five males and seven females, with biliary atresia were studied. In addition, four patients with progressive familial intrahepatic cholestasis and three with Alagille syndrome were also included. Five patients with neonatal hepatitis were studied as controls of a liver disease without portal fibrosis. Serum concentration of total and conjugated bilirubin, gamma-glutamyl transferase and glutamic-pyruvic transaminase were measured by routine methods in all patients at time of sampling for the study. The degree of fibrosis in liver biopsies was scored using the histologic activity index.


RESULTS
In our study IL-8 was detectable in 11 of 12 patients with biliary atresia with a median level of 262 pg/ml and a highly statistically significant difference (P < 0.0001) from controls. In patients with progressive familial intrahepatic cholestasis or with Alagille syndrome serum IL-8 levels were similarly elevated. In patients with neonatal hepatitis, IL-8 levels were marginally increased. Serum IL-8 levels were significantly correlated (Rs = 0.725, P < 0.0001) with the histologic activity index.


CONCLUSIONS
Although further studies are needed to determine the role of IL-8 in portal inflammation, our results suggest that increased production of IL-8 may be a mechanism leading to the progressive portal inflammation and fibrosis in patients with chronic liver disease.
Nobili
Valerio
V
Department of Liver Disease, Laboratory of Rheumatology, Research Institute, Bambino Gesu' Children's Hospital, Rome, Italy. v.nobili@libero.it
Marcellini
Matilde
M
Giovannelli
Luigi
L
Girolami
Elia
E
Muratori
Flaminia
F
Giannone
Germana
G
Devito
Rita
R
De Benedetti
Fabrizio
F
D001656:Biliary Atresia / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood*; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha