IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis
Abstract Background Interleukin-6 (IL-6) plays a central role in sepsis-induced cytokine storm involving immune hyperactivation and early neutrophil activation. Programmed death protein-1 (PD-1) is associated with sepsis-induced immunosuppression and lymphocyte apoptosis. However, the effects of sim...
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2025-01-01
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| Series: | BMC Immunology |
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| Online Access: | https://doi.org/10.1186/s12865-024-00679-z |
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| author | Song I Lee Na Young Kim Chaeuk Chung Dongil Park Da Hyun Kang Duk Ki Kim Min-Kyung Yeo Pureum Sun Jeong Eun Lee |
| author_facet | Song I Lee Na Young Kim Chaeuk Chung Dongil Park Da Hyun Kang Duk Ki Kim Min-Kyung Yeo Pureum Sun Jeong Eun Lee |
| author_sort | Song I Lee |
| collection | DOAJ |
| description | Abstract Background Interleukin-6 (IL-6) plays a central role in sepsis-induced cytokine storm involving immune hyperactivation and early neutrophil activation. Programmed death protein-1 (PD-1) is associated with sepsis-induced immunosuppression and lymphocyte apoptosis. However, the effects of simultaneous blockade of IL-6 and PD-1 in a murine sepsis model are not well understood. Results In this study, sepsis was induced in male C57BL/6 mice through cecal ligation and puncture (CLP). IL-6 blockade, PD-1 blockade, or combination of both was administered 24 h after CLP. Peripheral blood count, cytokine level, lymphocyte apoptosis in the spleen, neutrophil infiltration in the lungs and liver, and survival rate were measured. The mortality rate of the IL-6/PD-1 group was lower, though not statistically significant (p = 0.164), than that of CLP mice (75.0% vs. 91.7%). The IL-6/PD-1 group had lower neutrophil percentage and platelet count compared with the CLP group; no significant difference was observed in other cytokine levels. The IL-6/PD-1 group also showed reduced T lymphocyte apoptosis in the spleen and decreased neutrophil infiltration in the liver and lungs. Conclusions IL-6/PD-1 dual blockade reduces neutrophil infiltration, lymphocyte apoptosis, and bacterial burden while preserving tissue integrity in sepsis. Although the improvement in survival was not statistically significant, these findings highlight its potential as a therapeutic approach in sepsis. |
| format | Article |
| id | doaj-art-2ed5bf419bfb41218c6453952de0cc31 |
| institution | Kabale University |
| issn | 1471-2172 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj-art-2ed5bf419bfb41218c6453952de0cc312025-01-19T12:16:35ZengBMCBMC Immunology1471-21722025-01-0126111310.1186/s12865-024-00679-zIL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsisSong I Lee0Na Young Kim1Chaeuk Chung2Dongil Park3Da Hyun Kang4Duk Ki Kim5Min-Kyung Yeo6Pureum Sun7Jeong Eun Lee8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Chungnam National University HospitalDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Chungnam National University HospitalDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Chungnam National University HospitalDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Chungnam National University HospitalDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Chungnam National University HospitalDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Chungnam National University HospitalDepartment of Pathology, Chungnam National University School of MedicineCollege of Medicine, Research Institute for Medical Sciences, Chungnam National UniversityDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Chungnam National University HospitalAbstract Background Interleukin-6 (IL-6) plays a central role in sepsis-induced cytokine storm involving immune hyperactivation and early neutrophil activation. Programmed death protein-1 (PD-1) is associated with sepsis-induced immunosuppression and lymphocyte apoptosis. However, the effects of simultaneous blockade of IL-6 and PD-1 in a murine sepsis model are not well understood. Results In this study, sepsis was induced in male C57BL/6 mice through cecal ligation and puncture (CLP). IL-6 blockade, PD-1 blockade, or combination of both was administered 24 h after CLP. Peripheral blood count, cytokine level, lymphocyte apoptosis in the spleen, neutrophil infiltration in the lungs and liver, and survival rate were measured. The mortality rate of the IL-6/PD-1 group was lower, though not statistically significant (p = 0.164), than that of CLP mice (75.0% vs. 91.7%). The IL-6/PD-1 group had lower neutrophil percentage and platelet count compared with the CLP group; no significant difference was observed in other cytokine levels. The IL-6/PD-1 group also showed reduced T lymphocyte apoptosis in the spleen and decreased neutrophil infiltration in the liver and lungs. Conclusions IL-6/PD-1 dual blockade reduces neutrophil infiltration, lymphocyte apoptosis, and bacterial burden while preserving tissue integrity in sepsis. Although the improvement in survival was not statistically significant, these findings highlight its potential as a therapeutic approach in sepsis.https://doi.org/10.1186/s12865-024-00679-zActivation, LymphocyteActivation, NeutrophilInterleukin 6Sepsis |
| spellingShingle | Song I Lee Na Young Kim Chaeuk Chung Dongil Park Da Hyun Kang Duk Ki Kim Min-Kyung Yeo Pureum Sun Jeong Eun Lee IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis BMC Immunology Activation, Lymphocyte Activation, Neutrophil Interleukin 6 Sepsis |
| title | IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis |
| title_full | IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis |
| title_fullStr | IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis |
| title_full_unstemmed | IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis |
| title_short | IL-6 and PD-1 antibody blockade combination therapy regulate inflammation and T lymphocyte apoptosis in murine model of sepsis |
| title_sort | il 6 and pd 1 antibody blockade combination therapy regulate inflammation and t lymphocyte apoptosis in murine model of sepsis |
| topic | Activation, Lymphocyte Activation, Neutrophil Interleukin 6 Sepsis |
| url | https://doi.org/10.1186/s12865-024-00679-z |
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