Necrotic foci, elevated chemokines and infiltrating neutrophils in the liver of glycogen storage disease type Ia

JOURNAL OF HEPATOLOGY

卷:48

Article

Kim, So Youn¹  Weinstein, David A.²  Starost, Matthew F.³  Mansfield, Brian C.¹  Chou, Janice Y.¹ 

[1] NICHHD, Sect Cellular Differentiat, NIH, Bethesda, MD 20892 USA

[2] Univ Florida, Coll Med, Div Pediat Endocrinol, Glycogen Storage Dis Program, Gainesville, FL 32610 USA

[3] NIH, Div Vet Resources, Bethesda, MD 20892 USA

关键词: glycogen storage disease type Ia;    hepatic necrosis;    hepatic neutrophil infiltration;    chemokines;    hepatocellular adenoma;    glucose homeostasis;   

DOI  :  10.1016/j.jhep.2007.11.014

来源: Elsevier

【 摘 要 】

Background/Aims: Glycogen storage disease type la (GSD-Ia) patients manifest the long-term complication of hepatocellular adenoma (HCA) of unknown etiology. We showed previously that GSD-Ia mice exhibit neutrophilia and elevated serum cytokine levels. This study was conducted to evaluate whether human GSD-Ia patients exhibit analogous increases and whether in GSD-Ia mice a correlation exists between immune abnormalities and, biochemical and histological alterations in the liver. Methods: Differential leukocyte counts and cytokine levels were investigated in GSD-Ia patients. Hepatic chemokine production, neutrophil infiltration, and histological abnormalities were investigated in GSD-Ia mice. Results: We show that GSD-Ia patients exhibit increased peripheral neutrophil counts and serum interleukin-8 (IL-8). Compared to normal subjects, HCA-bearing GSD-Ia patients have a 2.8-fold higher serum IL-8 concentration, while GSD-Ia patients without HCA have a 1.4-fold higher concentration. Hepatic injury in GSD-Ia mice is evidenced by necrotic foci, markedly elevated infiltrating neutrophils, and increased hepatic production of chemokines. Conclusions: Peripheral neutrophilia and elevated serum chemokines are characteristic of GSD-Ia with HCA-bearing GSD-Ia patients having the highest serum IL-8. In GSD-Ia mice these elevations correlate with elevated hepatic chemokine levels, neutrophil infiltration, and necrosis. Taken together, peripheral neutrophilia and increased serum chemokines may indicate hepatic injuries in GSD-Ia. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.

【 授权许可】

Free