Proinflammatory cytokines, middle molecules, and drugs

Proinflammatory cytokines, middle molecules, and drugs refers to a heterogeneous group of pathological and exogenous substances targeted for removal from the blood during extracorporeal purification therapies, most notably hemoperfusion using adsorbent polymers like CytoSorb (Napp et al., 2022, Critical Care). Proinflammatory cytokines, such as Interleukin-6 (IL-6), Interleukin-8 (IL-8), and Tumor Necrosis Factor-alpha (TNF-alpha), are key signaling proteins that drive the hyperinflammatory cytokine storm associated with sepsis, COVID-19, and major surgery (Malard et al., 2018, Int J Artif Organs). Middle molecules are defined as solutes with molecular weights ranging from approximately 500 Da to 60 kDa, including uremic toxins like beta-2 microglobulin and endogenous proteins like myoglobin, which can lead to acute kidney injury and systemic toxicity (Rosenson et al., 2021, UpToDate). This category also encompasses specific drugs, particularly antithrombotic agents like ticagrelor and rivaroxaban, which may require rapid removal to manage life-threatening bleeding or to facilitate emergency surgery (Hassan et al., 2019, J Clin Med). These substances are not a single molecular target but are grouped together based on their susceptibility to removal via size-exclusion and hydrophobic adsorption (Malard et al., 2018). The primary therapeutic goal is to restore immunological and metabolic homeostasis by reducing the peak concentrations of these harmful mediators in the systemic circulation (Napp et al., 2022).

Other names

Middle moleculesInflammatory mediatorsUremic toxinsAdsorbable solutesCytokine storm mediators

Extracorporeal removal via surface adsorption and convective clearance