[Pharmacologic aspects of polyunsaturated fatty acids in parenteral nutrition]

Despite immense progress in intensive-care medicine, mortality rates of 30-70% in sepsis and SIRS are still an unresolved problem. Particularly the failure of respiratory and other vital functions is a major cause of death. Besides infectious stimuli (viruses, bacteria, fungi) a variety of non-infectious triggers (tissue damage, immune complexes, complement activation, etc.) can initiate the development of organ failure. These inflammatory reactions aim physiologically towards inactivation and removal of the stimulating agents as well as the induction of reparative processes. In states of prolonged activation of humoral and cellular mediator systems the natural host defence mechanisms react in an uncontrolled manner causing tissue damage and organ failure. So far there are no efficient therapeutic strategies to influence these complex inflammatory reactions. In the development of SIRS and sepsis, pro-inflammatory lipid mediators play a crucial role. Omega-3-fatty acids (omega-3-PUFAs) have shown anti-inflammatory and antithrombotic properties in a great number of experimental and clinical studies. These effects seem to be related to the uptake of eicosapentaenoic acid (EPA) into cellular membrane lipid pools and its subsequent metabolisation. After inflammatory activation EPA is released besides arachidonic acid (AA) and competes with AA for metabolisation via the cyclo- and lipoxygenase pathway. Compared to AA the derivatives of EPA have less pro-inflammatory and chemotactic characteristics. With regard to prophylactic and therapeutic consequences it appears reasonable to supplement omega-3-PUFAs to attenuate the inflammatory response by modulating the generation of lipid mediators during inflammation.