Hypercatabolism and Anti-catabolic Therapies in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome

Abstract

Owing to the development of intensive care units, many patients survive their initial insults but progress to chronic critical illness (CCI). Patients with CCI are characterized by prolonged hospitalization, poor outcomes, and significant long-term mortality. Some of these patients get into a state of persistent low-grade inflammation, suppressed immunity, and ongoing catabolism, which was defined as persistent inflammation, immunosuppression, and catabolism syndrome (PICS) in 2012. Over the past few years, some progress has been made in the treatment of PICS. However, most of the existing studies are about the role of persistent inflammation and suppressed immunity in PICS. As one of the hallmarks of PICS, hypercatabolism has received little research attention. In this review, we explore the potential pathophysiological changes and molecular mechanisms of hypercatabolism and its role in PICS. In addition, we summarize current therapies for improving the hypercatabolic status and recommendations for patients with PICS.

Hyaluronan with Different Molecular Weights Can Affect the Gut Microbiota and Pathogenetic Progression of Post-Intensive Care Syndrome Mice in Different Ways

“…Despite sufficient attention being given to post-intensive care syndrome (PICS) in recent years, research on its pathogenesis remains insufficient, and clinical treatment options are lacking. Although researchers have attempted to treat PICS using antibiotics [17,18] or anti-catabolic therapy [5], these approaches have not fully resolved the complex symptoms of immune system disorders, catabolic disorders, and insufficient nutritional intake [19]. The administration of stimulant drugs may even induce endogenous damage in patients [18].…”

“…The deterioration of intestinal function is the key factor that drives the worsening of patients' conditions [5]. There is a vicious cycle in patients with PICS, in which the continuous deterioration of the intestinal system seriously affects their health [5]. The deterioration of the intestinal system in the PICS mice was severe (Figure 2).…”

“…The intestinal system is the largest endocrine organ and the second largest immune system in the human body, closely linked to nutrient intake, immune regulation, and metabolism of substances and energy. Critically ill patients often experience dysfunction of the intestinal system due to ischemia resulting from sepsis, severe COVID-19, or other major illnesses [5]. This leads to a weakened intestinal barrier function, which in turn facilitates the translocation of gut bacteria or toxins and ultimately leads to endogenous damage to multiple organs [6].…”

“…At the same time, the ecosystem of the gut microbiota is also disrupted during this period, resulting in the dysregulation of the microbiota structure and function, further impairing intestinal function and exacerbating the patient's condition [7]. Jinlin Zhang et al proposed that damage to the structure and function of the intestinal system, as well as the disruption of the gut microbiota ecosystem, are important factors in the cycle of health deterioration in PICS patients (including intestinal function-immune regulation and catabolism) [5]. Based on this viewpoint, we hypothesis that the interventions targeting the gut microbiota to maintain intestinal system stability may be an effective means of improving PICS.…”

The prospects of interleukin-6 inhibition in rheumatoid arthritis: Olokizumab (novel monoclonal antibodies to IL-6)

“…11. Изучить возможности расширения показаний для терапии ОКЗ, учитывая позитивный опыт применения ингибиторов ИЛ-6 (ТЦЗ) для лечения гигантоклеточного артериита [131][132][133], артериита Такаясу [134], ювенильного идиопатического артрита [135], болезни Стилла взрослых [136], ранней системной склеродермии [112,113], аутовоспалительных заболеваний (семейная средиземноморская лихорадка, болезнь Бехчета, периодический синдром, ассоциированный с рецептором ФНО) [137], гипервоспалительных синдромов [120,138,139], включая синдром активации макрофагов, гемафагоцитарный лимфогистиоцитоз, CAR-T (Chimeric antigen receptor) клеточную терапию, COVID-19, синдром PICS (persistent infl ammation, immunosuppression, syndrome catabolism).…”