Immunotherapy of Sepsis: Blind Alley or Call for Personalized Assessment?

Abstract

Sepsis is the most frequent cause of death in noncoronary intensive care units. In the past 10 years, progress has been made in the early identification of septic patients and their treatment. These improvements in support and therapy mean that mortality is gradually decreasing, however, the rate of death from sepsis remains unacceptably high. Immunotherapy is not currently part of the routine treatment of sepsis. Despite experimental successes, the administration of agents to block the effect of sepsis mediators failed to show evidence for improved outcome in a multitude of clinical trials. The following survey summarizes the current knowledge and results of clinical trials on the immunotherapy of sepsis and describes the limitations of our knowledge of the pathogenesis of sepsis. Administration of immunomodulatory drugs should be linked to the current immune status assessed by both clinical and molecular patterns. Thus, a careful daily review of the patient's immune status needs to be introduced into routine clinical practice giving the opportunity for effective and tailored use of immunomodulatory therapy.

Detection of early cytokine storm in patients with septic shock after abdominal surgery

“…[32] The timing course of cytokine storms in this study could be used to explain the negative results from other studies that targeted cytokine storms during the treatment of sepsis. [33][34][35][36][37][38] One possible reason for the failure of BP therapy or immunotherapy in sepsis was that most of these studies did not dynamically monitor cytokine levels, did not accurately understand body's changing immune status, and missed the optimal opportunity for treatment. Cytokines may still be removed or suppressed even during the subsequent immunosuppressive phase.…”

Incidence, trends, and outcomes of infection sites among hospitalizations of sepsis: A nationwide study

“…In contrast, those infections with multiple protective barriers (such as skin, and musculoskeletal infections) had lower mortality rates [26]. This knowledge could be used to refine prognostication in sepsis helping to select patient populations that may benefit from novel treatments or that require higher levels of monitoring [27][28][29]. For example, it has been postulated that immunomodulatory agents failed to improve outcomes in septic patients in clinical trials because of enrolment of patients who have lower/intermediate risks or death [30].…”

Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced immunosuppression via enhancing autophagy

“…Sepsis is a life-threatening condition caused by a dysregulated host response to infection (Singer et al, 2016). In the last decade, reversing sepsis-induced immunosuppression becomes the focus of sepsis research instead of targeting cytokine storm (Cohen, 2002;Hotchkiss, Monneret & Payen, 2013a;Kox, Volk, Kox & Volk, 2000;Prucha, Zazula & Russwurm, 2017). However, drugs in current clinical trials, such as IL-7, anti-programmed cell death receptor-1 (anti-PD-1) and anti-PD-L1 antibodies, probably only for the immunosuppression stage of sepsis (Hotchkiss, Monneret & Payen, 2013a;Prucha, Zazula & Russwurm, 2017), and its clinical efficacy is yet to be proven.…”

“…Considering the drugs based on the inhibition of critical pro-inflammatory mediators have failed, the therapeutic strategy to improve immunosuppression is the focus of sepsis treatment now (Cohen, 2002;Hotchkiss, Monneret & Payen, 2013a;Kox, Volk, Kox & Volk, 2000;Prucha, Zazula & Russwurm, 2017).…”