Potential Pathophysiological Mechanisms Underlying Multiple Organ Dysfunction in Cytokine Release Syndrome

Table 1

Drugs commonly used to inhibit cytokine storms.

Distribution	Representative drug	Targets	CRS-related diseases	Effect	Regulatory approval status
Cytokine/cytokine; receptor antagonist	Clazakizumab	IL-6	Rejection of kidney; transplantation; COVID-19; Rheumatoid arthritis	DSA↓; IL-6↓; ACR20 response rate↑	Clinical trial
	Tocilizumab	IL-6R	COVID-19; Rheumatoid arthritis	All-cause mortality rate↓; ICU occupancy↓; ACR20/50/70 response rate↑	FDA
	Emapalumab	IFN-γ	pHLH; COVID-19	IFN-γ↓	FDA
	Canakinumab/Anakinra	IL-1/IL-1R	Macrophage activation; syndrome, rheumatoid; arthritis, COVID-19	IL-1β↓; Clinical symptoms are; relieved or under control	FDA
	Infliximab/adalimumab/; etanercept	TNF-α	COVID-19; Inflammatory bowel disease	TNF-α↓; IL-1↓; IL-6↓	FDA
Downstream; pathway blockers	Ruxolitinib	JAK-1, JAK-2	COVID-19	IL-10/IL-12/IL-23/TGF-β↓	FDA
	Phillyrin	NF-κB	COVID-19	Expression of proteins related to; NF-κB↓, IL-6↓, TNF-α↓,; IL-1β↓, IP-10↓, and MCP-1↓	Clinical trial
	Thiazolidinedione	PPAR-γ	Type 2 diabetic nephropathy	Inhibition of NF-κB	Clinical trial
	Fingolimod	S1PR	COVID-19	S1PR-1↓; TNF-α↓; IL-6↓	FDA
Other treatment	Dexamethasone	/	COVID-19 and systemic; immune disease	Inhibits a variety of cytokines	FDA
	Lianhuaqingwen capsule	/	COVID-19	Alleviates clinical symptoms; and shortens recovery time	NMPA
	Vitamin C	/	COVID-19	Inhibition of NF-κB IL-6↓; TNF-α↓; GM-CSF signaling response↓; Reduces oxidative stress	/
	Plasma of convalescent patients	SARS-COV-2	COVID-19	RNA of COVID-19↓	FDA (EUA)

FDA: Food and Drug Administration (America); NMPA: National Medical Products Administration (China); EUA: Emergency-Use-Administration; pHLH: primary hemophagocytic lymphohistiocytosis; DSA: donor-specific antibody; IL-6/IL-1: interleukin-6/interleukin-1; IL-6R/IL-1R: interleukin-6 receptor/interleukin-1 receptor; IFN-γ: interferon-γ; ACR20: American College of Rheumatology 20%, a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire (HAQ)), visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP); TNF-α: tumor necrosis factor-α; JAK-1/JAK-2: Janus kinase-1/Janus kinase-2; NF-κB: nuclear factor kappa-B; PPAR-γ: peroxisome proliferator-activated receptors; S1PR: sphingosine-1-phosphate receptor; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; GM-CSF: granulocyte-macrophage colony-stimulating factor.