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.
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.
Carter
C R D
CR
Division of Immunobiology, NIBSC, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK.
Dagg
B M
BM
Whitmore
K M
KM
Keeble
J R
JR
Asokanathan
C
C
Rodgers
A
A
Watanabe
M
M
Xing
D
D
Walker
K B
KB
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
D000336:Aerosols; D018664:Interleukin-12; D007371:Interferon-gamma