Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis Infection
Chronic use of statins may have anti-inflammatory action, promoting immunomodulation and survival in patients with sepsis. This study aimed to analyze the effects of pretreatment with simvastatin in lethal sepsis induced by cecal ligation and puncture (CLP). Male Swiss mice received prophylactic tre...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02137/full |
| _version_ | 1818480235350327296 |
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| author | Jose A. F. Braga Filho Afonso G. Abreu Afonso G. Abreu Carlos E. P. Rios Liana O. Trovão Dimitri Luz F. Silva Dalila N. Cysne Johnny R. Nascimento Johnny R. Nascimento Thiare S. Fortes Thiare S. Fortes Lucilene A. Silva Rosane N. M. Guerra Rosane N. M. Guerra Márcia C. G. Maciel Carlos H. Serezani Flávia R. F. Nascimento Flávia R. F. Nascimento |
| author_facet | Jose A. F. Braga Filho Afonso G. Abreu Afonso G. Abreu Carlos E. P. Rios Liana O. Trovão Dimitri Luz F. Silva Dalila N. Cysne Johnny R. Nascimento Johnny R. Nascimento Thiare S. Fortes Thiare S. Fortes Lucilene A. Silva Rosane N. M. Guerra Rosane N. M. Guerra Márcia C. G. Maciel Carlos H. Serezani Flávia R. F. Nascimento Flávia R. F. Nascimento |
| author_sort | Jose A. F. Braga Filho |
| collection | DOAJ |
| description | Chronic use of statins may have anti-inflammatory action, promoting immunomodulation and survival in patients with sepsis. This study aimed to analyze the effects of pretreatment with simvastatin in lethal sepsis induced by cecal ligation and puncture (CLP). Male Swiss mice received prophylactic treatment with simvastatin or pyrogen-free water orally in a single daily dose for 30 days. After this period, the CLP was performed. Naïve and Sham groups were performed as non-infected controls. Animal survival was monitored for 60 h after the CLP. Half of mice were euthanized after 12 h to analyze colony-forming units (CFUs); hematological parameters; production of IL-10, IL-12, IL-6, TNF-α, IFN-γ, and MCP-1; cell counts on peritoneum, bronchoalveolar lavage (BAL), bone marrow, spleen, and mesenteric lymph node; immunephenotyping of T cells and antigen presenting cells and production of hydrogen peroxide (H2O2). Simvastatin induced an increase in survival and a decrease in the CFU count on peritoneum and on BAL cells number, especially lymphocytes. There was an increase in the platelets and lymphocytes number in the Simvastatin group when compared to the CLP group. Simvastatin induced a greater activation and proliferation of CD4+ T cells, as well as an increase in IL-6 and MCP-1 production, in chemotaxis to the peritoneum and in H2O2 secretion at this site. These data suggest that simvastatin has an impact on the survival of animals, as well as immunomodulatory effects in sepsis induced by CLP in mice. |
| first_indexed | 2024-12-10T11:20:44Z |
| format | Article |
| id | doaj.art-271967e945a34bd5b0405cc82fb559b7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T11:20:44Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-271967e945a34bd5b0405cc82fb559b72022-12-22T01:50:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-09-01910.3389/fimmu.2018.02137390293Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis InfectionJose A. F. Braga Filho0Afonso G. Abreu1Afonso G. Abreu2Carlos E. P. Rios3Liana O. Trovão4Dimitri Luz F. Silva5Dalila N. Cysne6Johnny R. Nascimento7Johnny R. Nascimento8Thiare S. Fortes9Thiare S. Fortes10Lucilene A. Silva11Rosane N. M. Guerra12Rosane N. M. Guerra13Márcia C. G. Maciel14Carlos H. Serezani15Flávia R. F. Nascimento16Flávia R. F. Nascimento17Laboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilPrograma de Pós-Graduação em Ciências da Saúde, Federal University of Maranhão, São Luís, BrazilCEUMA University, São Luís, BrazilLaboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilLaboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilLaboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilLaboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilLaboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilPrograma de Pós-Graduação em Ciências da Saúde, Federal University of Maranhão, São Luís, BrazilLaboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilPrograma de Pós-Graduação em Ciências da Saúde, Federal University of Maranhão, São Luís, BrazilLaboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilLaboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilPrograma de Pós-Graduação em Ciências da Saúde, Federal University of Maranhão, São Luís, BrazilPrograma de Pós-Graduação em Ciências da Saúde, Federal University of Maranhão, São Luís, BrazilDivision of Infectious Diseases, Departments of Medicine, Pathology, Microbiology and Immunology, Institute for Infection, Immunology and Inflammation, Vanderbilt University School of Medicine, Nashville, TN, United StatesLaboratory of Immunophysiology, Federal University of Maranhão, São Luís, BrazilPrograma de Pós-Graduação em Ciências da Saúde, Federal University of Maranhão, São Luís, BrazilChronic use of statins may have anti-inflammatory action, promoting immunomodulation and survival in patients with sepsis. This study aimed to analyze the effects of pretreatment with simvastatin in lethal sepsis induced by cecal ligation and puncture (CLP). Male Swiss mice received prophylactic treatment with simvastatin or pyrogen-free water orally in a single daily dose for 30 days. After this period, the CLP was performed. Naïve and Sham groups were performed as non-infected controls. Animal survival was monitored for 60 h after the CLP. Half of mice were euthanized after 12 h to analyze colony-forming units (CFUs); hematological parameters; production of IL-10, IL-12, IL-6, TNF-α, IFN-γ, and MCP-1; cell counts on peritoneum, bronchoalveolar lavage (BAL), bone marrow, spleen, and mesenteric lymph node; immunephenotyping of T cells and antigen presenting cells and production of hydrogen peroxide (H2O2). Simvastatin induced an increase in survival and a decrease in the CFU count on peritoneum and on BAL cells number, especially lymphocytes. There was an increase in the platelets and lymphocytes number in the Simvastatin group when compared to the CLP group. Simvastatin induced a greater activation and proliferation of CD4+ T cells, as well as an increase in IL-6 and MCP-1 production, in chemotaxis to the peritoneum and in H2O2 secretion at this site. These data suggest that simvastatin has an impact on the survival of animals, as well as immunomodulatory effects in sepsis induced by CLP in mice.https://www.frontiersin.org/article/10.3389/fimmu.2018.02137/fullsimvastatinprophylactic treatmentsepsisimmunomodulationmacrophageshydrogen peroxide |
| spellingShingle | Jose A. F. Braga Filho Afonso G. Abreu Afonso G. Abreu Carlos E. P. Rios Liana O. Trovão Dimitri Luz F. Silva Dalila N. Cysne Johnny R. Nascimento Johnny R. Nascimento Thiare S. Fortes Thiare S. Fortes Lucilene A. Silva Rosane N. M. Guerra Rosane N. M. Guerra Márcia C. G. Maciel Carlos H. Serezani Flávia R. F. Nascimento Flávia R. F. Nascimento Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis Infection Frontiers in Immunology simvastatin prophylactic treatment sepsis immunomodulation macrophages hydrogen peroxide |
| title | Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis Infection |
| title_full | Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis Infection |
| title_fullStr | Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis Infection |
| title_full_unstemmed | Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis Infection |
| title_short | Prophylactic Treatment With Simvastatin Modulates the Immune Response and Increases Animal Survival Following Lethal Sepsis Infection |
| title_sort | prophylactic treatment with simvastatin modulates the immune response and increases animal survival following lethal sepsis infection |
| topic | simvastatin prophylactic treatment sepsis immunomodulation macrophages hydrogen peroxide |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02137/full |
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