[Pharmacological immunomodulation in sepsis]

Sepsis is defined as a dysregulated host response to infection; it is one of the leading causes of death in intensive care units worldwide. Immunological dysregulation plays a central role in the pathophysiology of sepsis and thus represents a promising therapeutic target for its treatment. However, the immune response is complex, and hyperinflammation and immune paralysis can occur simultaneously or sequentially, in different compartments, and with individually variable courses. Although a broad spectrum of immunomodulatory substances is available in principle, clinical trials have long yielded disappointing results. Growing evidence suggests that the cause of this lies less in the failure of individual substances than in the failure to account for the immunological heterogeneity of the clinical picture. This article provides a structured overview of pharmacological approaches to immunomodulation in sepsis, ranging from anti-inflammatory to immunostimulatory therapies. A particular focus is placed on biomarker-guided personalized immunotherapy. A prospective, multicenter, randomized study on this topic was recently published for the first time, which achieved a positive primary endpoint in sepsis patients through a personalized therapeutic approach, thereby paving the way for future sepsis therapy.