RESUMO
To determine the potentiality of prophylactic and/or therapeutic approaches using a traditional herbal medicine, Bu-zhong-yi-qi-tang (Japanese name: Hochu-ekki-to, HOT), for the control of allergic disease, we examined the effects of oral administration of HOT on a murine model of asthma allergic responses. When oral administration of HOT was begun at the induction phase immediately after OVA sensitization, eosinophilia and Th2-type cytokine production in the airway were reduced in OVA-sensitized mice following OVA inhalation. The serum levels of OVA-specific immunoglobulin (Ig)E and IgG1 were significantly decreased, whereas the level of OVA-specific IgG2a was increased. Interleukin (IL)-4 production by spleen T cells in response to OVA was significantly suppressed, while Interferon (IFN)-gamma production was increased in mice treated with HOT in the induction phase. On the other hand, HOT given in the eliciting phase induced a predominant Th2 response with increased IgE production in OVA-sensitized mice following OVA inhalation. These results suggest that the oral administration of HOT dichotomously modulates allergic inflammation in a murine model for asthma, thus offering a different approach for the treatment of allergic disorders.
Assuntos
Asma/tratamento farmacológico , Asma/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Administração Oral , Animais , Asma/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Interferon gama/biossíntese , Interleucina-4/biossíntese , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologiaRESUMO
We recently constructed IL-15 transgenic (Tg) mice using cDNA encoding a secretable isoform of the IL-15 precursor protein under the control of an MHC class I promoter. The IL-15 Tg mice exhibited resistance against a primary infection with Listeria monocytogenes. The numbers of memory CD8(+) T cells were markedly increased in the IL-15 Tg mice following Listeria infection accompanied by sustained IL-15 production. The increased CD44(+)CD8(+) T cells in the infected IL-15 Tg mice were not specialized to recognize Listeria-specific antigen but produced a large amount of IFN-gamma in response to bystander stimulation exogenous IL-15 in combination with IL-12. Furthermore, Listeria-specific Th1 response by CD4(+) T cells was significantly augmented in the IL-15 Tg mice compared with control mice following Listeria infection. In vivo depletion of the CD8(+) T cells by anti-CD8 monoclonal antibody and adoptive transfer of the T cells from naive IL-15 Tg mice indicated that the CD8(+) T cells functioned not only to eliminate bacteria at the early stage of infection but also to promote Th1 response to L. monocytogenes. Overexpression of IL-15 shed light on a novel role of memory CD8(+) T cells in early protection and promotion of Th1 response against a primary infection with L. monocytogenes.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica , Interleucina-15/fisiologia , Listeriose/imunologia , Transferência Adotiva , Animais , Antígenos de Bactérias/imunologia , Linfócitos T CD8-Positivos/transplante , Células Cultivadas , Interleucina-12/farmacologia , Interleucina-15/biossíntese , Interleucina-15/genética , Cinética , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/imunologia , Listeriose/microbiologia , Listeriose/terapia , Linfonodos/imunologia , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Peritônio/imunologia , Fenótipo , Taxa de Sobrevida , Subpopulações de Linfócitos T/classificaçãoRESUMO
IL-15, a pleiotropic cytokine, is involved in the inflammatory responses in various infectious and autoimmune diseases. We have recently constructed IL-15-transgenic (Tg) mice, which have an increased number of memory-type CD8+ T cells in the peripheral lymphoid tissues. In the present study, we found that eosinophilia and Th2-type cytokine production in the airway were severely attenuated in OVA-sensitized IL-15-Tg mice following OVA inhalation. IL-15-Tg mice preferentially developed Tc1 responses mediated by CD8+ T cells after OVA sensitization, and in vivo depletion of CD8+ T cells by anti-CD8 mAb aggravated the allergic airway inflammation in IL-15-Tg mice following OVA inhalation. Adoptive transfer of CD8+ T cells from OVA-sensitized IL-15-Tg mice into normal mice before OVA sensitization suppressed Th2 response to OVA in the normal mice. These results suggest that overexpression of IL-15 in vivo suppresses Th2-mediated-allergic airway response via induction of CD8+ T cell-mediated Tc1 response.