Modification of encephalomyocarditis virus-induced diabetes in mice by antiviral agents.

The current study used a murine model of diabetes induced by the D variant of encephalomyocarditis virus (DEMC) to determine the protective effect of exogenous antiviral agents. Antivirals, which were found to inhibit the development of DEMC virus cytopathic effect in L-929 cell monolayers, were administered intraperitoneally beginning 12 h prior to DEMC virus challenge. Arildone (500 mg/kg per day) or murine interferon (3.2 X 10(6) IU/kg per day) significantly reduced the incidence of hyperglycemia at 4 days after virus challenge. The incidences of hyperglycemia were 96% in untreated, 62% in arildone, and 0% in interferon treated mice. In other experiments we found that interferon (1.6 X 10(6) IU/kg per 12 h X 3) significantly protected mice against diabetes when administered at the time of virus infection or beginning 12 h afterwards. This effect was associated with reductions in average viral titers in the heart and pancreas of infected animals relative to untreated, infected mice. The results of these studies suggest that picornavirus induced diabetes may be prevented or ameliorated by the use of antiviral agents.

Immunological alterations in the lungs of mice following ozone exposure: changes in immunoglobulin levels and antibody-containing cells.

Ozone was added to the air of the environmental chambers containing specific pathogen-free mice. At levels of 0.5 and 0.8 ppm the oxidant was seen to have inflammatory effects, as shown by rising serum albumin levels in lung lavage fluid. Fluorescein conjugated anti-heavy chain sera were used to detect cells containing IgM, IgG, and IgA in measured lung areas termed Pulmonary Units. Antigenic stimuli occurred along the airways, with significant increases of IgA-containing cells in the bronchus-associated lymphoid tissue. The numbers of IgM- and IgG-containing cells did not increase. Immunodiffusion analyses for immunoglobulins in lung lavage fluid indicated increases of IgG1, IgG2, and IgA in lung secretions. The calculation of changing Ig/Alb ratios suggested that the IgA present was largely the result of local synthesis, while IgG molecules were mainly of serum origin. Possible sources of antigenic stimuli to ozone-exposed lungs are discussed.

Antibody responses and interferon titers in the respiratory tracts of mice after aerosolized exposure to influenza virus.

We studied the temporal appearance of immunoglobulins (immunoglobulins G1, G2, M, and A) and interferon in lung lavage fluids of mice after aerosol exposure to influenza virus in six animal groups in which mortality rates ranged from 0 to 24%. Immunoglobulin levels in the lung lavage fluids were markedly higher in mouse groups with higher mortality rates (16, 20, and 24%) than in those with low mortality rates (0, 2.5, and 7.5%). Analysis of serum albumin in the respiratory secretions as an index of edema indicated that increased immunoglobulin G levels during the early phase of infection were due to increased vascular permeability. The detection of virus-neutralizing antibodies and antibodies reactive with influenza virus antigens in the lavage fluids at 6 to 8 days postinfection suggested local immunoglobulin synthesis as a result of antigenic stimulation. Both systemic and local antibody productions contributed to immunoglobulin levels in the respiratory secretions after aerosolized influenza virus infection. Peak levels of interferon in the lavage fluids were reached before detection of significant levels of virus-neutralizing antibody in the serum or the lung lavage.