Liposomen-mediierter Gentransfer — die zukünftige Therapieform bei Sepsis und intraabdomineller Infektion?

Background: It is now generally accepted that over-production of pro-inflammatory cytokines (TNF-α, IL-1β) produced by inflammatory cells contributes to the pathological consequences of septic shock. Neutralizing this exaggerated immune response by monoclonal antibodies (anti-TNF-α), receptor antagonists (IL-1rα) and anti-inflammatory cytokines (IL-10) did not result in a better outcome in septic patients. Firstly, this is due to the short biological half-lives of these natural antagonists or inhibitors of pro-inflammatory cytokines. Secondly, exaggerated pro-inflammatory cytokine production may contribute to pathology in one body compartment while, simultaneously, the same mediators may have beneficial effects in another compartment. Thus, systemic administration of cytokine inhibitors at levels sufficient to neutralize exaggerated cytokine production in one organ may also block the presumably beneficial aspects of cytokine production in another. Methods: Our own results of animal experiments of the liposome mediated gene transfer are presented. Results: Liposome mediated gene transfer seems to be a promising low-risk alternative to systemic anti-inflammatory therapies as it ensures the local delivery of high doses of cytokine inhibitors and antagonists over a prolonged period of time. Conclusions: The pathophysiological mechanism of sepsis and septic shock are well established. The concept of local intervention or compartimental blockade of overwhelming mediator production by gene transfer will be a new challenge in the future.