A high-dose, short-duration treatment with ribavirin aerosol consisting of a three-fold increase in concentration of drug (60 mg versus 20 mg of ribavirin per mL in the liquid reservoir of the generator administered for about one-third the time of the standard treatment) was as effective as the standard dosage in the treatment of experimental influenza A and B infections in mice and in the treatment of experimental respiratory syncytial virus infection in cotton rats. Despite some minor pulmonary intolerance, it was considered to be suitable for use in treatment of patients with severe chronic pulmonary disease, and it was well-tolerated and apparently effective in the treatment (by face mask and endotracheal tube) of infants with bronchiolitis principally caused by respiratory syncytial virus infection. Pharmacokinetic studies in mice revealed very high concentrations of drug in the lungs, about triple the level with the standard dose, with similar blood and brain concentrations. Ribavirin concentrations were similarly high in respiratory secretions of infants given the triple dose.
Interleukin-1 (IL-1) production by blood monocytes and blastogenesis produced by tuberculin purified protein derivative (PPD) in blood T lymphocytes were examined in patients with pulmonary tuberculosis. Monocytes were isolated from blood mononuclear cells by plastic adherence, and IL-1 activity was determined in the mouse thymocyte proliferation assay. Monocytes from patients with tuberculosis produced significantly higher activities of IL-1 than did those from healthy tuberculin reactors when stimulated with lipopolysaccharide (LPS) (patients, 56.1 +/- 20.0 U/ml; healthy control subjects, 7.3 +/- 1.7 U/ml; p less than 0.05) or PPD (patients, 28.1 +/- 7.2 U/ml; healthy control subjects, 9.5 +/- 2.9 U/ml; p less than 0.05). In contrast, PPD-induced blastogenic responses in peripheral blood mononuclear cells (PBMC) from the patients were lower than those from healthy subjects (patients, 4,506 +/- 1,145 cpm; healthy control subjects, 14,655 +/- 2,240 cpm; p less than 0.005), and IL-1 production by monocytes showed a positive correlation with monocyte suppressor activity for PPD-induced blastogenesis. Moreover, exogenous IL-1 was capable of suppressing antigen-induced blastogenesis of PBMC from healthy subjects. These data suggest that monocytes from patients with pulmonary tuberculosis are activated to produce or secrete increased levels of IL-1 and that IL-1 may be a mediator of suppressor cell function.
