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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.
Carter, C R D; Dagg, B M; Whitmore, K M; Keeble, J R; Asokanathan, C; Rodgers, A; Watanabe, M; Xing, D; Walker, K B.
Affiliation
  • Carter CR; Division of Immunobiology, NIBSC, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK.
Cytokine ; 30(3): 100-8, 2005 May 07.
Article in En | MEDLINE | ID: mdl-15826816
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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Collection: 01-internacional Database: MEDLINE Main subject: Bordetella Infections / Killer Cells, Natural / Interferon-gamma / Interleukin-12 / Lung Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cytokine Journal subject: ALERGIA E IMUNOLOGIA Year: 2005 Document type: Article Country of publication:
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Collection: 01-internacional Database: MEDLINE Main subject: Bordetella Infections / Killer Cells, Natural / Interferon-gamma / Interleukin-12 / Lung Type of study: Prognostic_studies Limits: Animals Language: En Journal: Cytokine Journal subject: ALERGIA E IMUNOLOGIA Year: 2005 Document type: Article Country of publication: