Table 1.
A list of proinflammatory mediators causing cytokine storm in infectious diseases [34], [38], [39], [40], [41], [42], [43], [44].
| Cytokines/Chemokines | Source | Signaling Pathway | Action After Activation |
|---|---|---|---|
| Interleukin (IL)-1 | Macrophages, Dendritic cells, B- cells | Nuclear Factor Kappa -B (NF-κB) pathway, Toll Like Receptor (TLR) signaling pathway | Pro-inflammatory, proliferation and activation of Natural Killer cells (NK cells), T-cells and B-cells |
| IL-2 | T-cells | NF-κB pathway, TLR signaling pathway | proliferation and activation of NK cells, B- and T- cells |
| IL-4 | Th cells | NF-κB pathway, TLR signaling pathway | Stimulates synthesis of IgG and IgE antibodies, proliferation of B- cells and T cells |
| IL-6 (plays vital role in cytokine storm) | Macrophages, fibroblasts, Th cells. | NF-κB pathway, TLR signaling pathway | Stimulates synthesis of IgG antibodies |
| IL-7 | Epithelial cells, Stromal cells. | NF-κB pathway, TLR signaling pathway | T- and B- cell growth factor |
| IL-8 | Macrophages | NF-κB pathway, TLR signaling pathway | Chemotaxis |
| IL-9 | T-cell | NF-κB pathway, TLR signaling pathway | Growth and proliferation of T- cells |
| IL–11 | Bone marrow Stromal cells | NF-κB pathway, TLR signaling pathway | Differentiation of B- cells |
| IL −13 | T-cells | NF-κB pathway, TLR signaling pathway | Activation of NK cells |
| (Tumor necrosis factor) TNF – α | Macrophages | p38 MAPK | Activation of phagocytes |
| (Interferons) IFN – α |
Leukocytes | RIG-I | Shows anti-viral action |
| IFN – γ | RIG-I | Shows anti-viral action and activates monocytes, Neutrophils | |
| (Colony stimulating factors) G-CSF |
Endothelium and fibroblasts. | JAK/STAT pathway, MAPK pathway. | Synthesis of neutrophils, eosinophils and basophils (Granulocytes) |
| GM- CSF | T-cells, Fibroblasts and Macrophages | JAK/STAT pathway, MAPK pathway | Synthesis of granulocytes and monocytes |
| M- CSF | Endothelium and fibroblasts | JAK/STAT pathway, MAPK pathway | Monocyte production and activation |
| Chemokines CCL2/MCP-1 |
Osteoblasts, Macrophages, endothelial cells, adipocytes, fibroblast | NF-κB pathway, p38 MAPK pathway | Chemotaxis of macrophages, monocytes, dendritic cells, basophils, NK-cells, Myeloid cells into tissues |
| CCL3 (MIP-1α) | Monocytes, Dendritic cells, Lymphocytes, mononuclear phagocytes | p38 MAPK pathway | Chemotaxis of Monocytes, eosinophils, basophils, lymphocytes |
| CCL5 (RANTES) | Platelets, T cells, Eosinophils and Basophils | MAPK pathway | Chemotaxis of monocytes and T-lymphocytes |