High dose interleukin-12 exacerbates Bordetella pertussis infection and is associated with suppression of cell-mediated immunity in a murine aerosol challenge model
| Autor: | Dorothy Xing, K. M. Whitmore, J. R. Keeble, C. R. D. Carter, C. Asokanathan, Belinda Dagg, Kenneth Barry Walker |
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| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Bordetella pertussis
Cellular immunity Whooping Cough medicine.medical_treatment Immunology Spleen Enzyme-Linked Immunosorbent Assay Interferon-gamma Mice Immune system Immunity Immunopathology medicine Concanavalin A Immunology and Allergy Animals Lymphocytes Lung Cells Cultured Aerosols Immunity Cellular Mice Inbred BALB C biology biology.organism_classification Interleukin-12 Killer Cells Natural medicine.anatomical_structure Cytokine NG-Nitroarginine Methyl Ester Interleukin 12 Animal Studies Female Injections Intraperitoneal |
| Popis: | SUMMARYThe in -vivo clearance of Bordetella pertussis infections in murine models in naive mice and animals vaccinated with whole-cell vaccine is considered to be via a Th-1-dependent mechanism in which interleukin-12 (IL)-12 may play a prominent role. It has also been demonstrated clearly that the treatment of animals with macrophage-derived IL-12 administered with an acellular vaccine can increase the efficacy of this vaccine preparation to levels seen with the whole-cell vaccine. However, the effects of exogenously added IL-12 on immune responses in non-vaccinated B. pertussis-challenged mice remain unclear, with two studies giving contradictory findings. In this study we have treated mice with escalating doses of mIL-12 (0·1–10 µg/mouse) prior to challenge with B. pertussis (using an aerosol challenge model of infection). The ability of mice to clear infection was assessed in IL-12 treated and in phosphate buffered saline (PBS) control animals at days 6 and 13 post-challenge. Lymphoid cells were isolated from spleen and cell-mediated immune responses assessed at days 1, 6 and 13 post-challenge. In addition, the direct effects of high-dose IL-12 on challenged mice was assessed by checking natural killer (NK) activity from isolated lung and spleen lymphoid cells as well as interferon-γ (IFN-γ) generation from isolated cells and serum at day 1 post-challenge. The results from this study show that bacterial colonization of the lungs is actually enhanced following treatment with high-dose IL-12. This is associated with impaired cellular immune responses. The mechanisms associated with the immunosuppressive effects of IL-12 are discussed. |
| Databáze: | OpenAIRE |
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