Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes
| العنوان: | Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes |
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| المؤلفون: | Natalie E. Stevens, Cara K. Fraser, John D. Hayball, Kerrilyn R. Diener, Tim Kuchel, Marianne J. Chapman |
| المساهمون: | Stevens, Natalie E, Chapman, Marianne J, Fraser, Cara K, Kuchel, Tim R, Hayball, John D, Diener, Kerrilyn R |
| المصدر: | Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) Scientific Reports |
| بيانات النشر: | Nature Portfolio, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_treatment, Cohort Studies, Pathogenesis, Molecular Targeted Therapy, HMGB1 Protein, Cecum, Multidisciplinary, biology, Immunosuppression, Middle Aged, Shock, Septic, Treatment Outcome, Cytokine, Pseudomonas aeruginosa, Cytokines, Medicine, Female, experimental models of disease, medicine.symptom, Science, Inflammation, chemical and pharmacologic phenomena, Punctures, HMGB1, Article, Sepsis, 03 medical and health sciences, medicine, Animals, Humans, Ligation, Aged, Sheep, Innate immune system, Septic shock, business.industry, Macrophages, Dendritic Cells, medicine.disease, Survival Analysis, infection, Endotoxemia, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Immunology, biology.protein, business |
| الوصف: | Sepsis remains a significant health burden and a major clinical need exists for therapeutics to dampen the excessive and uncontrolled immune activation. Nuclear protein high mobility group box protein 1 (HMGB1) is released following cell death and is a late mediator in sepsis pathogenesis. While approaches targeting HMGB1 have demonstrated reduced mortality in pre-clinical models of sepsis, the impact of HMGB1 blockade on the complex septic inflammatory milieu and the development of subsequent immunosuppression remain enigmatic. Analysis of plasma samples obtained from septic shock patients established an association between increased HMGB1 and non-survival, higher APACHE II scores, and increased pro-inflammatory cytokine responses. Pre-clinically, administration of neutralising ovine anti-HMGB1 polyclonal antibodies improved survival in murine endotoxaemia and caecal ligation and puncture-induced sepsis models, and altered early cytokine profiles to one which corresponded to patterns observed in the surviving patient cohort. Additionally, anti-HMGB1 treated murine sepsis survivors were significantly more resistant to secondary bacterial infection and exhibited altered innate immune cell phenotypes and cytokine responses. These findings demonstrate that anti-HMGB1 antibodies alter inflammation in murine sepsis models and reduce sepsis mortality without potentiating immunosuppression. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7715df618c2a494624924e31846c3939 https://doaj.org/article/db850342f341408eaced7e104b682ab6 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7715df618c2a494624924e31846c3939 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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