Non-conventional immunomodulation in the management of sepsis

Sepsis remains a critical global health issue, demanding novel therapeutic strategies. Traditional immunomodulation treatments such as corticosteroids, specific modifiers of cytokines, complement or coagulation, growth factors or immunoglobulins, have so far fallen short. Meanwhile the number of studies investigating nonconventional immunomodulatory strategies is expanding. This review provides an overview of adjunctive treatments with herbal-based medicine, immunonutrition, vasopressors, sedative treatments and targeted temperature management, used to modulate the immune response in patients with sepsis. Herbal-based medicine, notably within traditional Chinese medicine, shows promise. Xuebijing injection and Shenfu injection exhibit anti-inflammatory and immune-modulatory effects, and the potential to lower 28-day mortality in sepsis. Selenium supplementation has been reported to reduce the occurrence of ventilatorassociated pneumonia among sepsis patients, but study results are conflicting. Likewise, the immunesuppressive effects of omega-3 fatty acids have been associated with improved clinical outcomes in sepsis. The immunomodulating properties of supportive treatments also gain interest. Vasopressors like norepinephrine exhibit dual dosage-dependent roles, potentially promoting both pro- and anti-inflammatory effects. Dexmedetomidine, a sedative, demonstrates anti-inflammatory properties, reducing sepsis mortality rates in some studies. Temperature management, particularly maintaining higher body temperature, has also been associated with improved outcomes in small scale human trials. In conclusion, emerging non-conventional immunomodulatory approaches, including herbal medicine, immunonutrition, and targeted supportive therapies, hold potential for sepsis treatment, but their possible implementation into everyday clinical practice necessitates further research and stringent clinical validation in different settings.