Circulating and tissue levels of the neutrophil chemotaxin interleukin-8 are elevated in severe acute alcoholic hepatitis, and tissue levels correlate with neutrophil infiltration

Abstract

Acute alcoholic hepatitis is characterized by a unique degree of liver neutrophil infiltration, often accompanied by marked peripheral neutrophilia in the absence of demonstrable bacterial or fungal infection. In this study we assayed plasma and tissue levels of a potent neutrophil activator and chemotaxin, interleukin-8, in patients with a spectrum of alcoholic liver diseases and in normal and diseased control subjects. Levels of circulating interleukin-8 were undetectable in normal subjects but highly elevated in patients with alcoholic hepatitis, particularly in those who died (geometric mean = 600 ng/L; confidence interval = 323 to 1,120 vs. geometric mean = 184 ng/L; confidence interval = 114 to 309 in survivors). Levels correlated with biochemical indicators of severe disease (bilirubin: R = 0.38; international prothrombin ratio: R = 0.28; white blood cell count: R = 0.35; creatinine: R = 0.34) and with tumor necrosis factor-alpha (R = 0.43) and soluble tumor necrosis factor receptors (p55; R = 0.59). In contrast, moderate elevations in the levels of circulating interleukin-8 were seen in alcoholic cirrhosis (geometric mean = 93 ng/L; confidence interval = 40 to 213) and in alcoholic patients undergoing alcohol withdrawal (geometric mean = 137 ng/L; confidence interval = 72 to 259). Levels in nonalcoholic inflammatory liver disease were comparatively low (geometric mean = 17 ng/L; confidence interval = 10 to 29).(ABSTRACT TRUNCATED AT 250 WORDS)

The CXC chemokine MIP-2 stimulates neutrophil mobilization from the rat bone marrow in a CD49d-dependent manner

“…[6][7][8][9][10][11] Experiments were performed using an in situ perfusion system of the rat femoral bone marrow. Thus, the chemokine rat MIP-2 was infused directly into the femoral bone marrow via the femoral artery, and mobilized leukocytes were collected via cannulation of the femoral vein.…”

“…It has been reported that plasma levels of CXC chemokines rise during inflammatory reactions and contribute to the acute release of neutrophils from the bone marrow. [6][7][8][9][10][11] Therefore, to mimic an inflammatory reaction we have infused a pulse of the CXC chemokine, rat macrophage inflammatory protein-2 (MIP-2) to stimulate an acute mobilization of neutrophils from the bone marrow.…”

Expression of C-C Chemokines is Associated with Portal and Periportal Inflammation in the Liver of Patients with Chronic Hepatitis C

“…Magnification: ϫ64 (a, d, and e), ϫ100 (c), and ϫ400 (b). as cirrhosis and alcoholic or autoimmune hepatitis, compared with those of normal controls (Sheron et al, 1993). In chronic hepatitis C, IL-8 -mRNA expression is also associated with a significant histological activity index (HAI) (Shimoda et al, 1998).…”

Interleukin-8 and hIRH (SDF1-α/PBSF) mRNA expression and histological activity index in patients with chronic hepatitis C

“…10 In certain pathological situations, IL-8 is produced excessively by a wide variety of cells and it is released in the circulation. Previous studies showed that IL-8 secretion or IL-8 gene expression in chronic or acute liver diseases such as cirrhosis and autoimmune or alcoholic hepatitis, were increased compared with normal controls, [13][14][15][16][17] but without attempts at defining which components of liver injury may be most affected.…”

“…11,12 Previous studies have shown that IL-8 secretion or IL-8 gene expression in chronic or acute liver disease, such as cirrhosis and alcoholic or autoimmune hepatitis, were increased compared with normal control groups. [13][14][15][16][17] However, the role of hIRH as well as IL-8 in the pathogenesis of hepatitis C virus (HCV)-related hepatitis remains unclear.…”