Multiorgan failure (MOF) represents the leading cause of death in patients with sepsis and systemic inflammatory response syndrome (SIRS) following severe trauma. The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. 1. Introduction In the 1970s, a syndrome of progressive, sequentially dysfunctional organ systems has been firstly characterized, eventually referred to as multiorgan failure (MOF) [1, 2]. As a predominant underlying condition, sepsis and sepsis-associated MOF represent one of the leading causes of death of hospitalized patients with reported morality rates ranging from 28% to 56% [3, 4]. Likewise, severe trauma and trauma-related multiorgan failure remain the leading cause of death in people below the age of 40 [5, 6]. The conception of organ failure has changed over the years and various scoring systems for the classification and diagnosis of MOF exist all of which attempt to quantify the degree of organ failure [7–9]. Currently, MOF is regarded as a continuous process of varying levels of organ failure rather than an all-or-none event [10]. To characterize MOF, six different organ systems are regarded as “key organs”: lungs, cardiovascular system, kidneys, liver, coagulation system, and central nervous system. Depending on the severity and various predisposing conditions, the initial insult (tissue trauma, infection) can induce a systemic host response that is characterized by the release of pro- and anti-inflammatory cytokines and metabolites (e.g., reactive oxygen (ROS) and nitrogen species (NOS)), activation of plasmatic cascade systems, such as the complement and the coagulation systems, and the appearance of acute phase proteins as well as hormonal and neuronal mediators [11–13]. Imbalanced systemic immune responses can ultimately lead to accumulation of leukocytes, disseminated intravascular coagulation (DIC), and microcirculatory dysfunction with subsequent apoptosis and necrosis of parenchymal cells, finally resulting in the development of MOF [12, 14, 15]. As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to
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