284 Chapter 11 Hyperinflammatory Immunoparalysis Cytokine production Ferritin (MAS-like) HLA-DR Cytokine release Metabolic dysfunction Recovery † † Homeostasis Anti-inflammatory Proinflammatory Immune Status Figure 2. Immune status. Disturbances in the homeostasis of the immune status are main causes of mortality. Inflammatory and anti-inflammatory processes are generally very effective for host defence but in sepsis these can become dysregulated and result in a loss-of-function to clear the pathogen or over activate protective host responses leading to an overwhelming inflammatory condition resulting in a gain-of-function of immune pathways. The exaggerated inflammatory response is characterized by increased cytokine production and the extreme of this spectrum is the macrophage activation syndrome (MAS). The loss-of function status is characterized by a decreased capacity to produce cytokines and loss of the capacity to activate the immune system (decrease in HLA-DR expression), and worse can even lead to a metabolic deficiency status of the immune cell. Sepsis is even more complex since both components, namely a loss-of-function and a gain-of-function of the immune response can co-exist. Adapted from reference [10].
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