Table 1.
Common inflammatory mediators and immune cells involved in cytokine storm.
| Mediato | Origin | Action, function and mechanism |
|---|---|---|
| Cytokines and growth factors | ||
| IL-1 | Macrophages, epithelial cells; pyroptotic cells | Pro-inflammatory alarmin cytokine; pyrogenic activity, activates macrophage and Th17 cell [190] |
| IL-2 | T cells | Effector T-cell and regulatory T-cell growth factor [191] |
| IL-6 | Macrophages, T cells, endothelial cells | Pyrogenic cytokine with pro-inflammatory activity, stimulate acute-phase reactions and antibody production[192] |
| IL-9 | Th9 cells | Defence against helminth infections, activates mast cells, association with type I interferon in COVID-19 [125], [193] |
| IL-10 | Regulatory T cells, Th9 cells | Anti-inflammatory cytokine; inhibit Th1 and cytokine release[194] |
| IL-12 | Dendritic cells, macrophages | Th1 pathway activation; induce Th1 cells for INF-γ release; activate CTLs and NK cells; show synergism with IL-18 [195] |
| IL-17 | Th17 cells, NK cells, group 3 innate lymphoid cells | Activate and propagate neutrophilic inflammation; protect against infections[196] |
| IL-18 | Monocytes, macrophages, dendritic cells | Alarmin cytokine with pro-inflammatory function; activation of Th1 pathway, exhibit synergism with IL-12 [197] |
| IL-33 | Macrophages, dendritic cells, mast cells, epithelial cells | Pro-inflammatory cytokine with alarmin function; potentiates Th1 and Th2 cells, NK cells, CTLs, and mast cells [198] |
| INF-γ | Th1, CTLs, group 1 innate lymphoid and NK cells | Pro-inflammatory cytokine; macrophages stimulation [125], [168] |
| TNF | Macrophages, T cells, NK cells, mast cells | Pro-inflammatory cytokine with pyrogenic function, increase vascular permeability[168] |
| GM-CSF | Th17 cells | Pro-inflammatory cytokine [199] |
| VEGF | Macrophages | Promotes angiogenesis [200], [201] |
| Chemokines | ||
| IL-8 (CXCL8) | Macrophages, epithelial cells | Chemotactic agent of neutrophils [202], [203] |
| MIG (CXCL9) | Monocytes, endothelial cells, keratinocytes | INF-stimulated chemokine; employment of Th1 cells, NK cells, plasmacytoid dendritic cells [24], [105] |
| IP-10 (CXCL10) | Monocytes, endothelial cells, keratinocytes | Recruitment of macrophages, Th1 cells, NK cells; INF-induced chemokine [204], [205] |
| MCP-1 (CCL2) | Macrophages, dendritic cells, cardiac myocytes | Chemotactic agent of Th2 cells, monocytes, dendritic cells, basophils [206], [207] |
| MIP-1α (CCL3) | Monocytes, neutrophils, dendritic cells, NK cells, mast cells | Chemotactic agent of macrophages, Th1 cells, NK cells, eosinophils, dendritic cells; pyrogenic function [207] |
| MIP-1β (CCL4) | Macrophages, neutrophils, endothelium | Recruitment of macrophages, Th1 cells, NK cells, dendritic cells [208] |
| BLC (CXCL13) | B cells, follicular dendritic cells | Recruitment of B cells, CD4+ T cells, dendritic cells [209] |
| Plasma proteins | ||
| CRP | Hepatocytes | Monomeric CRP increases IL-8 and MCP-1 production; IL-6 induced upregulated expression of CRP [186], [210] |
| Complement | Hepatocytes, other cells | Amplify tissue damage in cytokine storm; suppression of complement system abrogates pathophysiological effects of cytokine storm [211], [212] |
| Ferritin | Ubiquitous | Primary intracellular storage site of iron [210], [213] |
Note: BLC B-lymphocyte chemoattractant; COVID-19 coronavirus disease 2019; CRP C-reactive protein; CTLs cytotoxic T lymphocytes; CXCL C-X-C motif chemokine ligand; GM-CSF granulocyte–macrophage colony-stimulating factor; IP-10 interferon-inducible protein 10; MCP-1 monocyte chemoattractant protein 1; MIG monokine induced by interferon-γ; MIP-1α and MIP-1β macrophage inflammatory protein 1α and 1β, respectively; NK natural killer; Th helper T cells and VEGF vascular endothelial growth factor.