Pathogenesis and Treatment of Cytokine Storm Induced by Infectious Diseases

Abstract

Cytokine storm is a phenomenon characterized by strong elevated circulating cytokines that most often occur after an overreactive immune system is activated by an acute systemic infection. A variety of cells participate in cytokine storm induction and progression, with profiles of cytokines released during cytokine storm varying from disease to disease. This review focuses on pathophysiological mechanisms underlying cytokine storm induction and progression induced by pathogenic invasive infectious diseases. Strategies for targeted treatment of various types of infection-induced cytokine storms are described from both host and pathogen perspectives. In summary, current studies indicate that cytokine storm-targeted therapies can effectively alleviate tissue damage while promoting the clearance of invading pathogens. Based on this premise, “multi-omics” immune system profiling should facilitate the development of more effective therapeutic strategies to alleviate cytokine storms caused by various diseases.

Macrophages: shapes and functions

“…Any missing, delayed, or incomplete termination of an inflammatory reaction against pathogens, cell debris, or the like can lead to fatal adverse effects from macrophages. Failure to appropriately terminate an inflammatory response, in the worst case, can lead to an excessive recruitment/activation of immune cells and the excessive production and release of cytokines, also referred to as “cytokine storm” or “cytokine release syndrome” (CRS) [ 67 ]. As currently defined, cytokine storm is a condition associated with elevated systemic cytokine levels, systemic clinical signs of inflammation, and severe secondary tissue damage [ 16 ].…”

“…As excellently reviewed in [ 16 ], a cytokine storm can be induced by pathogenic invasive infectious disease [ 58 , 73 ] or as a side effect of chimeric antigen receptor T-cell (CAR-T) cell therapy [ 27 , 52 ], a recent cancer immunotherapy approach. Depending on the triggering agent, the induced cytokine profile can be of different composition [ 67 ]. While, e.g., CRS caused by SARS leads to the predominant release of IL-1β, IL-6, IL-12, IFNγ, IP10, and MCP-1 [ 6 ], COVID-19-associated CRS [ 56 ] has been characterized by increased release of IL-2, IL-7, IL-10, G-CSF, IP10, MCP-1, MIP-1α, and TNFα [ 29 ].…”

Ponciri Fructus Immaturus ethanol extract attenuates septic shock through inhibition of the STAT1 signaling pathway

“…Macrophage-mediated proinflammatory responses to infection generally allow pathogen clearance with minimal tissue damage and remodeling. However, the uncontrolled inflammatory response of macrophages causes excessive cytokine production, which can lead to local and systemic inflammation ( 30 ). TNF-α is a critical mediator of immune response to sepsis.…”

Possibility of averting cytokine storm in SARS-COV 2 patients using specialized pro-resolving lipid mediators

“…Cytokine storm can be triggered by pathogens, monogenic and autoimmune conditions, cancers/cancer therapy i.e. Iatrogenic and the most recent coronavirus disease 2019(Covid-19) [250] . Clinical symptoms vary, mostly all patients are febrile.…”