Treatment of mice with IL-12 DNA constructs leads to augmented NK activity in lungs but low IFN-gamma release -- implications for Bordetella pertussis infections following aerosol challenge |
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Authors: | Carter C R D Dagg B M Whitmore K M Keeble J R Asokanathan C Rodgers A Watanabe M Xing D Walker K B |
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Affiliation: | Division of Immunobiology, NIBSC, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK. |
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Abstract: | Interleukin-12 protein has been widely used experimentally in therapeutic and adjuvant settings in the treatment of different diseases including intra-cellular bacterial infections. The in vivo clearance of Bordetella pertussis infections in naive mice and in animals vaccinated with whole cell vaccine is considered to be a Th-1 dependent mechanism. Furthermore, the addition of IL-12 protein to an acellular pertussis vaccine increases the efficacy of this vaccine. Whilst the use of IL-12 protein is often beneficial, a number of problems there are associated with this cytokine including toxicities and down regulation of normal immune functions. The use of DNA constructs encoding this cytokine may be a way of achieving maximum therapeutic benefit with minimum toxicity. The aims of this study were to optimise the effects of two IL-12 DNA constructs, especially with respect to augmenting pulmonary immune responsiveness and to compare the effect of IL-12 DNA and IL-12 protein on bacterial colonisation of lungs following aerosol challenge with B. pertussis. We found that IL-12 DNA constructs augmented the activity of pulmonary NK cells but had little effect on the course of B. pertussis infections in mice. In contrast to IL-12 protein, the DNA constructs had no immunosuppressive effects on splenic lymphocyte mitogen responses. |
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