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→Mechanism of Acute Inflammation
However, in the case of acute inflammation, the response to an infection is dysregulated and often disproportional to the severity of the infection. The response gets overheated, overactivated, and can damage the body from within. Potential consequences of this overly strong reaction include infections, organ dysfunction (severe sepsis), or septic shock which is a state of circulatory failure where circulatory, cellular and metabolic abnormalities are associated with an increased risk of death. These reactions are often caused by coagulation (i.e. formation of blood clots) dysregulation. The hypercoagulability of sepsis is thought to be driven by the release of tissue factor from disrupted endothelial cells.<ref name="Arti13">Sepsis: The evolution in definition, pathophysiology, and management. SAGE Open Medicine, 7, 2050312119835043–2050312119835043, 2019, Gyawali, B., Ramakrishna, K., & Dhamoon, A. S., https://doi.org/10.1177/2050312119835043 </ref> When the human body suffers from severe sepsis, activated monocytes and endothelial cells, along with circulating microvesicles, become sources of tissue factor<ref name="Arti14">Role of extracellular vesicles in the development of sepsis-induced coagulopathy. Journal of Intensive Care, 6, 68, 2018, Iba, T., & Ogura, H., https://doi.org/10.1186/s40560-018-0340-6 </ref>.
This factor then causes the systemic activation of the coagulation cascade resulting in the production of thrombin, activation of platelets, and formation of platelet–fibrin clots. These structures can result in local perfusion defects leading to tissue hypoxia and organ dysfunction <ref name="Arti13">Sepsis: The evolution in definition, pathophysiology, and management. SAGE Open Medicine, 7, 2050312119835043–2050312119835043, 2019, Gyawali, B., Ramakrishna, K., & Dhamoon, A. S., https://doi.org/10.1177/2050312119835043 </ref>. Moreover, research has shown that dysregulated apoptotic immune cell-death plays a crucial part in immune dysfunction and mortality of sepsis. Apoptosis is a “programmed cell death” to limit damage of surrounding tissue during the immune response<ref name="Arti15">Apoptosis: a review of programmed cell death. Toxicologic Pathology, 35(4), 495–516, 2007, Elmore, S., https://doi.org/10.1080/01926230701320337 </ref>. It is a vital component of many processes in the human body such as cell turnover, proper development and functioning of the immune system <ref name="Arti15">Apoptosis: a review of programmed cell death.<ref name="Arti15">Apoptosis: a review of programmed cell death. Toxicologic Pathology, 35(4), 495–516, 2007, Elmore, S., https://doi.org/10.1080/01926230701320337 </ref> Most cells that undergo enhanced apoptosis in sepsis are of lymphoid origin, hence less immune cells are left to fight off the infection itself <ref name="Arti16">Host–pathogen interactions in sepsis. The Lancet Infectious Diseases, 8(1), 32–43, 2008, van der Poll, T., & Opal, S. M., https://doi.org/https://doi.org/10.1016/S1473-3099(07)70265-7 </ref>. Since no effective treatment for sepsis exists yet, early diagnosis and recognition is crucial.<ref name="Arti17">Sepsis and septic shock: current approaches to management. Internal Medicine Journal, 49(2), 160–170., 2019, Thompson, K., Venkatesh, B., & Finfer, S., https://doi.org/10.1111/imj.14199 </ref>
This is where IL-6 plays an important part. As mentioned, IL-6 is a cytokine that functions as a crucial mediator during the acute phase of response to inflammation in sepsis.<ref name="Arti18">Diagnostic and prognostic value of interleukin-6, pentraxin 3, and procalcitonin levels among sepsis and septic shock patients: a prospective controlled study according to the Sepsis-3 definitions. BMC Infectious Diseases, 19(1), 968, 2019, Song, J., Park, D. W., Moon, S., Cho, H.-J., Park, J. H., Seok, H., & Choi, W. S., https://doi.org/10.1186/s12879-019-4618-7 </ref> Research on the clinical value of IL-6 in patients with sepsis and septic shock describes that IL-6 is considered controversial regarding its diagnostic and prognostic values, where meta-analysis of diagnostic value of IL-6 has shown that IL-6 only offers moderate success in differentiating sepsis from non-infectious systemic inflammatory response syndrome (SIRS).<ref name="Arti19">Role of interleukin-6 to differentiate sepsis from non-infectious systemic inflammatory response syndrome. Cytokine, 88, 126–135, 2016, Ma, L., Zhang, H., Yin, Y.-L., Guo, W.-Z., Ma, Y.-Q., Wang, Y.-B., Shu, C., & Dong, L.-Q., https://doi.org/10.1016/j.cyto.2016.08.033 </ref> Hence it is recommended that IL-6 is used as a biomarker to confirm infection rather than differentiate between sepsis and SIRS<ref name="Arti19">Role of interleukin-6 to differentiate sepsis from non-infectious systemic inflammatory response syndrome. Cytokine, 88, 126–135, 2016, Ma, L., Zhang, H., Yin, Y.-L., Guo, W.-Z., Ma, Y.-Q., Wang, Y.-B., Shu, C., & Dong, L.-Q., https://doi.org/10.1016/j.cyto.2016.08.033 </ref>.