Summary of the biological function of biomarkers that were significantly elevated in severe cytokine release syndrome, in sepsis, in both or in neither
| Name . | Cells that secrete; function . | Name . | Cells that secrete; function . |
|---|---|---|---|
| Cytokines significantly more elevated in severe CRS as compared with sepsis | |||
| IFNγ | T cells, NK cells; activates macrophages, induces MHC II expression | GM-CSF | Macrophages, T-cells, NK cells; promotes macrophage and eosinophil proliferation |
| IL6 | T cells, B cells, monocytes; stimulates acute phase reactants | IL8 | Macrophages, epithelial cells, endothelial cells; induces chemotaxis |
| IP10 (CXCL10) | Monocytes, endothelial cells, fibroblasts; Secreted in response to IFNγ | MCP1 | Monocytes, macrophages; chemoattractant |
| sIL2Ra | Activated T and B cells; associated with mononuclear cell activation | MIG (CXCL9) | T-cells, NK cells, macrophages, NKT cells; chemotactic, induces differentiation of leukocytes, cell extravasation |
| IL10 | Monocytes, T cells; anti-inflammatory cytokine | IL13 | T-cells, mast cells, NKT cells; induce macrophage activation |
| HGF | Mesenchymal cells; growth and motility factor | MIP1β | Macrophages, monocytes; induce release of IL1, IL6, TNFα |
| sTNFRII | T cells, endothelial cells; pro-inflammatory cytokine | sCD163 | Monocytes, macrophages; marker of macrophage activation |
| IFNα | NK-, NKT-, T-cells; activates macrophages | VEGF | Many cells; endothelial permeability mediator |
| sgp130 | Present in sera; inhibits soluble IL6 | ||
| Cytokines significantly more elevated in sepsis as compared with severe CRS | |||
| FGF-Basic | Basement membrane and blood vessels; growth factor involved in angiogenesis | EGF | Epithelial cells; stimulates cell growth and differentiation |
| sIL1RI | Activated mononuclear cells, neutrophils; involved in IL2 and IL6 production | sIL4R | T-cells, basophils, eosinophils; TH2 lymphocyte differentiation, blocks binding of IL4 |
| sCD30 | Activated T-cells and TH-cells; TH2 immune response, elevated in some malignancies | IL1β | Activated macrophages; pyrogenic, inflammatory response |
| Cytokines similarly elevated in sepsis and severe CRS | |||
| IL2 | T-cells; promotes differentiation | ICAM1 | Endothelial cells, macrophages, lymphocytes; induced by IL1, TNFα, facilitates transmigration |
| sTNFRI | Multiple cell types; induces apoptosis in monocytes, antagonizes circulating TNFα | ANG2 | Endothelial and smooth muscle cells; increased by TNFα and VEGF |
| IL15 | Mononuclear cells; proliferation of NK cells | sVEGFR1 | Multiple cell types; angiogenesis inhibitor |
| MIP1α | Macrophages; recruitment and activation of granulocytes | sVEGFR3 | Multiple cell types; lymphangiogenesis inhibitor |
| sRAGE | Multiple cells; innate immune system activation | IL1Ra | Multiple cell types; mediates IL1 activation |
| Cytokines not elevated in sepsis or severe CRS | |||
| IL17 | TH17 cells; promotes inflammation | sVEGFR2 | Multiple cell types; lymphangiogenesis inhibitor |
| Eotaxin | Endothelial cells; chemotaxis for eosinophils | IL12 | Dendritic cells, macrophages; induces IFNγ |
| GCSF | Endothelial cells, macrophages; production of neutrophils and hematopoietic stem cells | IL5 | TH2 cells, mast cells; stimulates IgA secretion |
| IL4 | Basophils; differentiates TH cells to TH2 cells | RANTES | Platelets, fibroblasts; chemokine for T-cells, eosinophils, induces NK cells |
| IL7 | Marrow stromal cells; stimulates production of lymphoid progenitors | sIL6R | Activated T-cells; buffer to block IL6 signaling |
| TNFα | Macrophages, monocytes; acute phase reactant | sIL1RII | Monocytes, neutrophils, macrophages, T-cells; decoy receptor, regulates IL1RI |
| sEGFR | Multiple cells; growth factor | ||
| Name . | Cells that secrete; function . | Name . | Cells that secrete; function . |
|---|---|---|---|
| Cytokines significantly more elevated in severe CRS as compared with sepsis | |||
| IFNγ | T cells, NK cells; activates macrophages, induces MHC II expression | GM-CSF | Macrophages, T-cells, NK cells; promotes macrophage and eosinophil proliferation |
| IL6 | T cells, B cells, monocytes; stimulates acute phase reactants | IL8 | Macrophages, epithelial cells, endothelial cells; induces chemotaxis |
| IP10 (CXCL10) | Monocytes, endothelial cells, fibroblasts; Secreted in response to IFNγ | MCP1 | Monocytes, macrophages; chemoattractant |
| sIL2Ra | Activated T and B cells; associated with mononuclear cell activation | MIG (CXCL9) | T-cells, NK cells, macrophages, NKT cells; chemotactic, induces differentiation of leukocytes, cell extravasation |
| IL10 | Monocytes, T cells; anti-inflammatory cytokine | IL13 | T-cells, mast cells, NKT cells; induce macrophage activation |
| HGF | Mesenchymal cells; growth and motility factor | MIP1β | Macrophages, monocytes; induce release of IL1, IL6, TNFα |
| sTNFRII | T cells, endothelial cells; pro-inflammatory cytokine | sCD163 | Monocytes, macrophages; marker of macrophage activation |
| IFNα | NK-, NKT-, T-cells; activates macrophages | VEGF | Many cells; endothelial permeability mediator |
| sgp130 | Present in sera; inhibits soluble IL6 | ||
| Cytokines significantly more elevated in sepsis as compared with severe CRS | |||
| FGF-Basic | Basement membrane and blood vessels; growth factor involved in angiogenesis | EGF | Epithelial cells; stimulates cell growth and differentiation |
| sIL1RI | Activated mononuclear cells, neutrophils; involved in IL2 and IL6 production | sIL4R | T-cells, basophils, eosinophils; TH2 lymphocyte differentiation, blocks binding of IL4 |
| sCD30 | Activated T-cells and TH-cells; TH2 immune response, elevated in some malignancies | IL1β | Activated macrophages; pyrogenic, inflammatory response |
| Cytokines similarly elevated in sepsis and severe CRS | |||
| IL2 | T-cells; promotes differentiation | ICAM1 | Endothelial cells, macrophages, lymphocytes; induced by IL1, TNFα, facilitates transmigration |
| sTNFRI | Multiple cell types; induces apoptosis in monocytes, antagonizes circulating TNFα | ANG2 | Endothelial and smooth muscle cells; increased by TNFα and VEGF |
| IL15 | Mononuclear cells; proliferation of NK cells | sVEGFR1 | Multiple cell types; angiogenesis inhibitor |
| MIP1α | Macrophages; recruitment and activation of granulocytes | sVEGFR3 | Multiple cell types; lymphangiogenesis inhibitor |
| sRAGE | Multiple cells; innate immune system activation | IL1Ra | Multiple cell types; mediates IL1 activation |
| Cytokines not elevated in sepsis or severe CRS | |||
| IL17 | TH17 cells; promotes inflammation | sVEGFR2 | Multiple cell types; lymphangiogenesis inhibitor |
| Eotaxin | Endothelial cells; chemotaxis for eosinophils | IL12 | Dendritic cells, macrophages; induces IFNγ |
| GCSF | Endothelial cells, macrophages; production of neutrophils and hematopoietic stem cells | IL5 | TH2 cells, mast cells; stimulates IgA secretion |
| IL4 | Basophils; differentiates TH cells to TH2 cells | RANTES | Platelets, fibroblasts; chemokine for T-cells, eosinophils, induces NK cells |
| IL7 | Marrow stromal cells; stimulates production of lymphoid progenitors | sIL6R | Activated T-cells; buffer to block IL6 signaling |
| TNFα | Macrophages, monocytes; acute phase reactant | sIL1RII | Monocytes, neutrophils, macrophages, T-cells; decoy receptor, regulates IL1RI |
| sEGFR | Multiple cells; growth factor | ||
MHC, major histocompatibility complex; NK, natural killer; TH, T-helper.