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An experimental animal model is described in which small injections of antigen (SRBC) into the portal venous system of the rat produces a reduced immune response in comparison with that obtained following similar injection into the inferior vena cava. The difference in humoral response, measured by circulating haemagglutinins and haemolysins was only detectable after repeated doses of antigen. The dose of SRBC necessary to demonstrate this difference is shown to be critical. Cell-mediated immunity-determined by measuring ear swelling 24 hours after intra-auricular injection of antigen-could be demonstrated in animals immunized via the inferior vena cava but not in those immunized via the portal vein. Labelling of the antigen with radioactive chromium (5Cr) showed that the increased immune response to inferior vena cava injected antigen was accompanied by a reduced hepatic uptake of antigen, but no significant alteration in splenic uptake. [ABSTRACT FROM AUTHOR]

Background: The use of aerosol delivery of antimycobacterial agents for the therapy of tuberculosis in mice has not been well studied. Aerosol therapy in mice is problematic due to the high cost of the required apparatus. The purpose of this study was to explore the efficacy of intranasal (IN) administration (as a surrogate for aerosol delivery) of isoniazid (INH) and rifalazil (RZL) in a murine tuberculosis model compared to oral delivery. Methods & Materials: Six week old female Balb/c mice (purchased from Charles River Laboratories, Wilmington, MA) were infected intranasally with about 10³ CFU of Mycobacterium tuberculosis (MTB) ATCC 27294 (H37Rv) for experiment 1 or about 106 CFU of MTB ATCC 35801 (Erdman) for experiment 2. One week post infection mice in experiment 1 were treated withINH5mg/kg orally by gavage or 5mg/kg IN for 3 days and mice in experiment 2 were treated with RZL 5 mg/kg orally by gavage 5 days/week or 5 mg/kg IN Mon, Wed, and Fri for 2 weeks. At the initiation of therapy in each experiment a group of mice (early controls) were euthanized by CO2 inhalation and their lungs were collected. At the completion of therapy an untreated group of mice, late controls (LC), and treated mice were euthanized. Mycobacterial loads in right lungs were measured by serial dilution and plating on Middlebrook 7H10 agar plates. Results: The mycobacterial loads (log CFU) for the EC, LC, INH oral and INH IN were 3.34, 4.49, 2.94, and 2.82 respectively (exp. 1). The mycobacterial loads for the EC, LC, RZL oral, and RZL IN were 6.26, 8.93, 4.30, and 4.58 respectively (exp. 2). The LC group was euthanized 3 days early due to their advanced illness. IN delivery of INH and RIF was significantly better than the untreated late controls. Conclusion: The activities of INH and RZL by IN delivery in these experiments suggest that other agents that cannot be given orally could be evaluated for their potential therapeutic activities by IN administration. [ABSTRACT FROM AUTHOR]