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Dobson, G. P., Biros, E., Letson, H. L., & others. (2020). Living in a Hostile World: Inflammation, New Drug Development, and Coronavirus. Frontiers in immunology, 11. Added by: Dr. Enrique Feoli (17/07/2022, 15:41) Last edited by: Dr. Enrique Feoli (17/04/2025, 21:18) |
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| Resource type: Journal Article DOI: 10.3389/fimmu.2020.610131 ID no. (ISBN etc.): 1664-3224 BibTeX citation key: Dobson2020a View all bibliographic details  |
Categories: BioAcyl Corp, BioAcyl Corp, BioAcyl Corp Subcategories: Heridas quirúrgicas, Inflammation resolution, SSI China Creators: Biros, Dobson, Letson, others Collection: Frontiers in immunology |
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| Abstract |
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We present a brief history of the immune response and show that Metchnikoff’s theory of inflammation and phagocytotic defense was largely ignored in the 20th century. For decades, the immune response was believed to be triggered centrally, until Lafferty and Cunningham proposed the initiating signal came from the tissues. This shift opened the way for Janeway’s pattern recognition receptor theory, and Matzinger’s danger model. All models failed to appreciate that without inflammation, there can be no immune response. The situation changed in the 1990s when cytokine biology was rapidly advancing, and the immune system’s role expanded from host defense, to the maintenance of host health. An inflammatory environment, produced by immune cells themselves, was now recognized as mandatory for their attack, removal and repair functions after an infection or injury. We explore the cellular programs of the immune response, and the role played by cytokines and other mediators to tailor the right response, at the right time. Normally, the immune response is robust, self-limiting and restorative. However, when the antigen load or trauma exceeds the body’s internal tolerances, as witnessed in some COVID-19 patients, excessive inflammation can lead to increased sympathetic outflows, cardiac dysfunction, coagulopathy, endothelial and metabolic dysfunction, multiple organ failure and death. Currently, there are few drug therapies to reduce excessive inflammation and immune dysfunction. We have been developing an intravenous (IV) fluid therapy comprising adenosine, lidocaine and Mg2+ (ALM) that confers a survival advantage by preventing excessive inflammation initiated by sepsis, endotoxemia and sterile trauma. The multi-pronged protection appears to be unique and may provide a tool to examine the intersection points in the immune response to infection or injury, and possible ways to prevent secondary tissue damage, such as that reported in patients with COVID-19.
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| Notes |
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Without inflammation there is no immune response. Changes in the inflammatory milieu and low oxygen drives the type and extent of the immune response. Metchnikoff’s theory of inflammation and phagocytotic defense was largely ignored throughout the 20th century. In the 1990s, the role of the immune system expanded from defense to maintaining host health, which includes a low-level of inflammation associated with general housekeeping functions and maintenance of whole body steady-state. The adaptive response proceeds only if there is sufficient antigen to drive the process. In severe cases, inflammation can spread to become a systemic response and activate a CNS-sympathetically-driven “fight-or-flight” stress response, and if not controlled, can escalate into widespread immune, cardiovascular and metabolic dysfunction, multiple organ failure and death. Molecules that fulfill the criteria of pro-resolving mediators include specialized lipid mediators (lipoxins, resolvins, protectins, and maresins) (126, 166), proteins and peptides (annexin A1, adrenocorticotropic hormone), gaseous mediators (H2S and CO), purines (adenosine), as well as neuromodulators (acetylcholine and other neuropeptides) released under the control of the vagus nerve (126, 165, 167–169). Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
