Complement is one of the most ancient defense systems. It gets strongly activated immediately after acute
injuries like
trauma,
burn, or
sepsis and helps to initiate regeneration. However, uncontrolled complement activation contributes to
disease progression instead of supporting healing. Such effects are perceptible not only at the site of injury but also systemically, leading to systemic activation of other intravascular cascade systems eventually causing dysfunction of several vital organs. Understanding the
complement pathomechanism and its interplay with other systems is a strict requirement for exploring novel therapeutic intervention routes. Ex vivo models exploring the cross-talk with other systems are rather limited, which complicates the determination of the exact pathophysiological roles that
complement has in
trauma,
burn, and
sepsis. Literature reporting on these three conditions is often controversial regarding the importance, distribution, and temporal occurrence of complement activation products further hampering the deduction of defined pathophysiological pathways driven by
complement. Nevertheless, many in vitro experiments and animal models have shown beneficial effects of
complement inhibition at different levels of the cascade. In the future, not only inhibition but also a
complement reconstitution
therapy should be considered in prospective studies to expedite how meaningful
complement-targeted interventions need to be tailored to prevent
complement augmented multi-organ failure after
trauma,
burn, and
sepsis.This review summarizes clinically relevant studies investigating the role of
complement in the
acute diseases trauma,
burn, and
sepsis with important implications for clinical translation.