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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>.
