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[Therapeutic strategies against mediators of septic shock]
1Institutsbereich Medizinische Klinik, Forschungsinstitut Borstel.
Abstract:
The growing knowledge on the pathophysiological role of cytokines in septic shock stimulated efforts to control their synthesis and action pharmacologically in clinical situations. Among the various compounds elaborated by monocytes/macrophages in response to endotoxins, tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) have been recognized to be of particular importance for endotoxic effects. Therefore, therapeutic strategies in septic shock may benefit from antagonism or inhibition of these mediators. Anti-TNF-antibodies as well as pentoxifylline, an inhibitor of TNF synthesis, attenuated lethality provoked by endotoxin or sepsis in experimental animals. Furthermore, application of IL-1 receptor antagonist was able to counteract endotoxicity in animals. Based on these promising findings, controlled clinical studies have been started to define the precise clinical efficacy of the a.m. therapeutic strategies.
Insights
Targeting cytokines like tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1) shows promise in treating septic shock. Inhibiting these inflammatory mediators reduced mortality in animal models, leading to clinical trials.
Area of Science:
- Immunology
- Pharmacology
Context:
- Septic shock involves complex pathophysiological processes driven by inflammatory mediators.
- Cytokines, particularly tumor necrosis factor alpha (TNF) and interleukin-1 (IL-1), play a crucial role in the detrimental effects of endotoxemia.
Purpose:
- To explore the potential of pharmacologically controlling cytokine synthesis and action in managing septic shock.
- To evaluate therapeutic strategies targeting TNF and IL-1 in preclinical and clinical settings.
Summary:
- Knowledge of cytokine roles in septic shock has spurred drug development efforts.
- Anti-TNF antibodies and pentoxifylline (a TNF synthesis inhibitor) reduced mortality in animal models of endotoxemia and sepsis.
- Interleukin-1 (IL-1) receptor antagonist also demonstrated efficacy in counteracting endotoxicity in animal studies.
Impact:
- Preclinical success suggests that targeting TNF and IL-1 could be a viable therapeutic strategy for septic shock.
- Controlled clinical studies are underway to ascertain the efficacy of these anti-cytokine therapies in human patients.