It is well established that sepsis is associated with the systemic inflammatory response syndrome (SIRS), defined by the main presence of pro-inflammatory mediators in the plasma (e.g. TNFa, IL-1, IL-6, IL-8, etc.). The phenomenon could be due to excessive local generation of mediators or loss of control in the generation of inflammatory mediators. In fact, both appear to be responsible for SIRS. The compensatory antiinflammatory response syndrome (CARS) features increased levels of antiinflammatory interleukins (IL-4, IL-10, IL-13, etc.), which can function to inhibit the inflammatory response during sepsis (4,20) (Fig. 1).
In CLP-induced sepsis, generation of inflammatory proteins is indicated by the presence of inflammatory mediators in the peritoneal cavity (21,22), presumably caused by local activation of macrophages. In addition, organ and plasma levels of the anti-inflammatory interleukins, IL-4, IL-10 and IL-13, are altered, for reasons unknown (23,24). IL-4 and IL-10 are potent antiinflammatory mediators that suppress generation of pro-inflammatory mediators by blocking activation of or by modulating both the transcription and stability of specific mRNAs (25). The disturbance of these anti-inflammatory interleukins implies that gene activation leading to
Figure 1. Perturbed inflammatory response during sepsis
Figure 1. Perturbed inflammatory response during sepsis production of pro-inflammatory mediators is relatively uncontrolled, resulting in unregulated expression of these powerful mediators. It has been suggested that the sepsis syndrome is in part due to the lack of CARS, i.e., generation of regulatory interleukins with anti-inflammatory potency (20). There is no doubt that the "unhindered" presence in plasma of potent proinflammatory mediators such as TNFa and IL-1 during sepsis is an indication that control of the inflammatory response has been lost, resulting in a serious compromise of homeostasis (Figure 1).
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