Publicação
Immunomodulatory effects and protection of moxifloxacin in sepsis
| Resumo: | Sepsis is a complex syndrome that results from a harmful systemic inflammatory response to infection. It is the leading cause of death in Intensive Care Units, excluding neurotrauma, and the third most important cause of death in the hospital. However, it remains poorly understood, and in fact, in the past decades there have been no substantial advances in the treatment of this condition. As TNF-α and IL-1β are two important initial mediators of sepsis, immunomodulatory agents may be useful in the treatment of sepsis. Here we show that moxifloxacin, a fourth-generation fluoroquinolone with a broad antibacterial spectrum, has immunodulatory effects both in an in vitro assay and in a mice model of sepsis. Moxifloxacin protects against severe sepsis in mice, reducing the levels of cytokines and organ lesion markers. Moreover, our findings demonstrate that its actions are not due to its antibacterial effect and that its interaction with topoisomerase II or IV may not be relevant for the observed effects. The molecular mechanisms that explain its immunomodulatory effects remain unknown, and are certainly an interesting topic for future studies. |
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| Autores principais: | Velho, Tiago Rodrigues |
| Assunto: | IL-1β TNF-α Sepsis Moxifloxacin |
| Ano: | 2014 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Sepsis is a complex syndrome that results from a harmful systemic inflammatory response to infection. It is the leading cause of death in Intensive Care Units, excluding neurotrauma, and the third most important cause of death in the hospital. However, it remains poorly understood, and in fact, in the past decades there have been no substantial advances in the treatment of this condition. As TNF-α and IL-1β are two important initial mediators of sepsis, immunomodulatory agents may be useful in the treatment of sepsis. Here we show that moxifloxacin, a fourth-generation fluoroquinolone with a broad antibacterial spectrum, has immunodulatory effects both in an in vitro assay and in a mice model of sepsis. Moxifloxacin protects against severe sepsis in mice, reducing the levels of cytokines and organ lesion markers. Moreover, our findings demonstrate that its actions are not due to its antibacterial effect and that its interaction with topoisomerase II or IV may not be relevant for the observed effects. The molecular mechanisms that explain its immunomodulatory effects remain unknown, and are certainly an interesting topic for future studies. |
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