interleukin-8 and Encephalitis--Japanese

The ability of Japanese encephalitis virus (JEV) and JEV-induced macrophage derived neutrophil chemotactic factor (MDF) to produce nitric oxide (NO), and the possible antiviral effect of NO during JEV infection, was investigated. Splenic macrophages of JEV infected mice produced maximum NO in vivo at day 7 post infection, and in vitro at 24 h after JEV stimulation. MDF-induced NO production was dose dependent and maximal at 60 min after MDF treatment. The response was sensitive to anti-MDF antibody treatment and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Pretreatment of mice with L-NMMA increased the mortality to 100% in JEV infected mice in vivo and inhibited NO production in vitro, while MDF stimulated macrophages inhibited virus replication with high levels of NO production. MDF treatment increased the survival rate of JEV infected mice. The findings thus demonstrate that MDF induces production of NO during JEV infection, which has an antiviral effect. This may be one of the important mechanisms of natural immunity in controlling the initial stages of JEV infection.

Topics: Animals; Antiviral Agents; Cell Culture Techniques; Encephalitis Virus, Japanese; Encephalitis, Japanese; Immune Sera; Interleukin-8; Mice; Mice, Inbred Strains; Nitric Oxide; omega-N-Methylarginine; Spleen; Survival Rate; Virus Replication

Japanese encephalitis (JE) virus infection induces infiltration of neutrophils in neural as well as extraneural tissues in patients. As interleukin-8 (IL-8) has inflammatory properties, the present study was undertaken to investigate the IL-8 concentrations in cerebrospinal fluid (CSF) and serum from patients with JE and correlate them with neutrophil counts. IL-8 was measured in the CSF or serum of 30 patients with confirmed JE. The majority (92%) of the acute CSF samples showed raised levels of IL-8 with raised numbers of polymorphonuclear leucocytes. Similarly, significantly higher serum IL-8 concentrations were detected in the acute phase of illness than in convalescent JE patients or normal healthy controls. Twenty-one of 25 patients with high concentrations of IL-8 showed significantly increased neutrophil counts in acute phase sera. A gradual decline in neutrophil counts was observed in the convalescent phase of patients who recovered. There was a significant correlation between IL-8 level and the severity of illness, as all severely ill and fatal cases showed higher levels of IL-8 in acute CSF or serum than the levels found in those who recovered. IL-8 concentrations remained high for a longer period in patients with prolonged severe illness than in those who made a complete recovery.

Topics: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Convalescence; Encephalitis, Japanese; Humans; Interleukin-8; Leukocyte Count; Neutrophils

In this study, viruria following Japanese encephalitis virus (JEV) infection in mice has been shown to appear earlier in pregnant than in normal mice with proteinuria and haematuria. This was related to the production of splenic macrophage derived neutrophil chemotactic factor (MDF) following JEV infection. Intravenous inoculation of MDF in mice resulted in leakage of cells, proteins and erythrocytes in the urine as a result of altered capillary permeability. The isolation of virus from kidney did not correlate with the shedding of virus in the urine. The histological examination of sections of kidneys showed no morphological damage; however, ultrastructural degenerative changes in the mesangial cells were observed following JEV infection. These data suggest that JEV-induced macrophage derived factor regulates the leakage of proteins, erythrocytes and cells into the urine.

Topics: Acute Disease; Animals; Antibodies, Viral; Chemotaxis, Leukocyte; Encephalitis Virus, Japanese; Encephalitis, Japanese; Female; Fluorescent Antibody Technique; Hematuria; Interleukin-8; Kidney; Mice; Pregnancy; Pregnancy Complications, Infectious; Proteinuria; Spleen

The vascular effects of Japanese encephalitis virus (JEV)-stimulated splenic macrophage-derived neutrophil chemotactic factor (MDF) were evaluated in mice. Intraperitoneal injection of MDF in mice resulted in a rapid increase in capillary permeability in a dose-dependent manner as assessed by leakage of intravenously injected radiolabelled albumin ([125I]-albumin) or Evans blue dye. Intradermal inoculation of MDF in rabbits caused [51Cr]-labelled neutrophil emigration and accumulation into injected sites. Peak plasma leakage and neutrophil infiltration were observed at 1 h following MDF inoculation, and plasma leakage was restored by 2.5 h. The increase in capillary permeability was sensitive to pretreatment of mice with avil and ranitidine (H1 and H2 histamine receptor blockers, respectively), resulting in abrogation of the response; indomethacin, a prostaglandin synthetase inhibitor, did not have any effect.

Topics: Animals; Capillary Permeability; Chemotaxis, Leukocyte; Encephalitis, Japanese; Indomethacin; Interleukin-8; Macrophages; Mice; Neutrophils; Pheniramine; Ranitidine; Spleen

The mechanism of neutrophil leucocytosis in cases of Japanese encephalitis is not known. We here report that during Japanese encephalitis virus (JEV) infection in mice the splenic macrophages secrete a chemotactic factor that attracts the neutrophils. The peak activity of macrophage derived factor (MDF) was observed on day 7 following infection. The MDF acted in a dose-dependent manner. This chemoattractant was purified by low pressure liquid chromatography and gave a single band of 10 kD on silver stained polyacrylamide gel. The MDF was found to be heat resistant and sensitive to prolonged incubation with proteases.

Topics: Animals; Chemotaxis, Leukocyte; Encephalitis Virus, Japanese; Encephalitis, Japanese; Interleukin-8; Macrophage Activation; Macrophages; Mice; Spleen

Depression of serum iron following Japanese encephalitis virus (JEV) infection was observed in mice. The hypoferraemia was associated with the accumulation of iron in reticulo-endothelial cells in the spleen. Splenectomy (compared with sham-operation) prevented the depression in serum iron concentration after JEV infection. It also prevented the rise in levels of liver iron. The effect of JEV-stimulated, splenic macrophage-derived factor (MDF) was evaluated in causing hypoferraemia. MDF produced a rapid reduction in the serum iron levels with accumulation of iron in spleen. These observations suggest that MDF plays a key role in the regulation of iron metabolism during JEV infection.

Topics: Animals; Cytokines; Encephalitis, Japanese; Hemoglobins; Immune Sera; Interleukin-8; Iron; Liver; Macrophages; Male; Mice; Mice, Inbred Strains