Showing papers by "Atsushi Enomoto published in 1997"

Serum levels of IL-10, IL-15 and soluble tumour necrosis factor-alpha (TNF-α) receptors in type C chronic liver disease

Abstract: We previously reported that the number of TNF-α-producing cells was increased in the liver of patients with type C chronic liver disease. To understand further the pathophysiology of this change, we examined serum levels of two soluble TNF receptors, TNF-αRI (p55) and -αRII (p75), and IL-10, all of which act as TNF-α buffer, and IL-15, a novel cytokine sharing many immunological activities with IL-2, using ELISA methods. We studied control individuals and patients with type C chronic liver disease, including asymptomatic hepatitis C virus (HCV) carriers with persistently normal serum ALT values, and those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Both types of sTNF-αR closely correlated with disease progression. Patients with LC and HCC had significantly elevated levels for sTNF-αRII compared with the other patient groups and controls. Serum IL-10 levels were significantly greater in all chronic liver disease groups than in controls. With respect to IL-15, the values were high in CH, LC and HCC compared with those of controls. Notably, HCC patients showed highest values for both IL-10 and IL-15, with significant differences from the other patient groups. Serial determinations revealed that interferon (IFN) treatment for CH patients resulted in the suppression of circulating IL-10 and IL-15 levels along with decrease in serum aminotransferase values. Both cytokines remained at decreased levels after cessation of therapy in patients who went into clinical and virological remission. On the other hand, treatment did not affect serum levels of sTNF-αRs. These findings indicate that serum levels of these molecules correlated with disease progress in chronic HCV infection, and that IL-10 and IL-15 may reflect the degree of inflammation in the liver. It is also suggested that both cytokines may be related to the development of HCC.

Predominant appearance of NK1.1+ T cells producing IL-4 may be involved in the increased susceptibility of mice with the beige mutation during Salmonella infection.

Abstract: C57BL/6 mice with the beige mutation (beige mice) showed a high susceptibility to infection with Salmonella choleraesuis compared with C57BL/6 (B6) control mice, as assessed by bacterial number in the peritoneal cavity and the liver. The appearance of NK1.1+ CD3- NK cells was significantly suppressed, while NK1.1+ T cells were increased in the peritoneal cavity of beige mice after Salmonella infection. The expression level of IL-4 mRNA was much higher in freshly isolated NK1.1+ T cells of the infected beige mice, but the expression level of IFN-gamma mRNA was lower than that in the infected control mice. The NK1.1+ T cells produced more IL-4 in response to TCR alphabeta cross-linking, whereas IFN-gamma production upon TCR triggering was significantly impaired in the beige mice compared to that in the control mice. Furthermore, the generation of Salmonella-specific Th1 cells producing IFN-gamma was significantly inhibited in the peritoneal cavity of beige mice after Salmonella infection. However, administration of anti-IL-4 neutralizing mAb to beige mice during salmonellosis restored the generation of Salmonella-specific Th1 cells and decreased the susceptibility to Salmonella. These results suggested that the predominant activation of NK1.1+ T cells producing IL-4 over those producing IFN-gamma may be at least partly involved in the poor generation of Salmonella-specific protective Th1 cells, resulting in the increased susceptibility of beige mice to Salmonella infection.