Table 1. Soluble Mediators in Cytokine Storm.*.
| Mediator | Main Cell Source | Type and Function |
|---|---|---|
| Cytokines and growth factors | ||
| Interleukin-1 | Macrophages, epithelial cells; pyroptotic cells | Proinflammatory alarmin cytokine; pyrogenic function, macrophage and Th17 cell activation |
| Interleukin-2 | T cells | Effector T-cell and regulatory T-cell growth factor |
| Interleukin-6 | Macrophages, T cells, endothelial cells | Proinflammatory cytokine; pyrogenic function, increased antibody production, induction of acute-phase reactants |
| Interleukin-9 | Th9 cells | Protection from helminth infections, activation of mast cells, association with type I interferon in Covid-1926 |
| Interleukin-10 | Regulatory T cells, Th9 cells | Antiinflammatory cytokine; inhibition of Th1 cells and cytokine release |
| Interleukin-12 | Dendritic cells, macrophages | Activation of the Th1 pathway; induction of interferon-γ from Th1 cells, CTLs, and NK cells; acting in synergy with interleukin-18 |
| Interleukin-17 | Th17 cells, NK cells, group 3 innate lymphoid cells | Promoting neutrophilic inflammation, protection from bacterial and fungal infections |
| Interleukin-18 | Monocytes, macrophages, dendritic cells | Proinflammatory alarmin cytokine; activation of Th1 pathway, acting in synergy with interleukin-12 |
| Interleukin-33 | Macrophages, dendritic cells, mast cells, epithelial cells | Proinflammatory alarmin cytokine; amplification of Th1 and Th2 cells, activation of NK cells, CTLs, and mast cells |
| Interferon-γ | Th1 cells, CTLs, group 1 innate lymphoid cells, and NK cells | Proinflammatory cytokine; activation of macrophages |
| Tumor necrosis factor | Macrophages, T cells, NK cells, mast cells | Increasing vascular permeability; pyrogenic function |
| GM-CSF | Th17 cells | Proinflammatory cytokine |
| VEGF | Macrophages | Angiogenesis |
| Chemokines | ||
| Interleukin-8 (CXCL8) | Macrophages, epithelial cells | Recruitment of neutrophils |
| MIG (CXCL9) | Monocytes, endothelial cells, keratinocytes | Interferon-inducible chemokine; recruitment of Th1 cells, NK cells, plasmacytoid dendritic cells |
| IP-10 (CXCL10) | Monocytes, endothelial cells, keratinocytes | Interferon-inducible chemokine; recruitment of macrophages, Th1 cells, NK cells |
| MCP-1 (CCL2) | Macrophages, dendritic cells, cardiac myocytes | Recruitment of Th2 cells, monocytes, dendritic cells, basophils |
| MIP-1α (CCL3) | Monocytes, neutrophils, dendritic cells, NK cells, mast cells | Recruitment of macrophages, Th1 cells, NK cells, eosinophils, dendritic cells; pyrogenic function |
| MIP-1β (CCL4) | Macrophages, neutrophils, endothelium | Recruitment of macrophages, Th1 cells, NK cells, dendritic cells |
| BLC (CXCL13) | B cells, follicular dendritic cells | Recruitment of B cells, CD4 T cells, dendritic cells† |
| Plasma proteins | ||
| CRP | Hepatocytes | Monomeric CRP increases interleukin-8 and MCP-1 secretion; interleukin-6 increases CRP expression |
| Complement | Hepatocytes, other cells | Complement activation contributes to tissue damage in cytokine storm; complement inhibition can reduce immunopathologic effects of cytokine storm |
| Ferritin | Ubiquitous | Primary site of iron storage in cells |
*
BLC denotes 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; Th1, Th2, Th9, and Th17 cells types 1, 2, 9, and 17 helper T cells, respectively; and VEGF vascular endothelial growth factor.
†
In idiopathic multicentric Castleman’s disease, the levels of CXCL13 are the most elevated of all the cytokines or chemokines.