title: 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.
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.
authors.affiliation: Division of Immunobiology, NIBSC, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK.
authors.forename: C R D
authors.initials: CR
authors.lastname: Carter
authors.forename: B M
authors.initials: BM
authors.lastname: Dagg
authors.forename: K M
authors.initials: KM
authors.lastname: Whitmore
authors.forename: J R
authors.initials: JR
authors.lastname: Keeble
authors.forename: C
authors.initials: C
authors.lastname: Asokanathan
authors.forename: A
authors.initials: A
authors.lastname: Rodgers
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: D
authors.initials: D
authors.lastname: Xing
authors.forename: K B
authors.initials: KB
authors.lastname: Walker
mesh_terms: D000336:Aerosols; D000818:Animals; D001885:Bordetella Infections / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001886:Bordetella pertussis / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D007167:Immunotherapy; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014917:Whooping Cough / Q000276:immunology / Q000628:therapy
chemical_list: D000336:Aerosols; D018664:Interleukin-12; D007371:Interferon-gamma