Table 1.
Cyto/Chemokines: potent contributors of MG pathogenesis.
| Cyto/Chemokines | Main cellular sources | Regulation | MG associated major function | Treatment Responses | Ref. | |
|---|---|---|---|---|---|---|
| Up | Down | |||||
| TNF | Monocyte, Th1, Mφ | ↑ | Proinflammatory | Conditional | (15, 33–37) | |
| IL-1β | Macrophages | ↑ | Proinflammatory | Unknown | (38) | |
| IL-4 | Th2, mast cells, eosinophils, basophils | ↓ | Pleiotropic antiinflammatory cytokine | Present | (38, 39) | |
| IL-6/IL-6R | Monocyte, | ↑ | Proinflammatory | Present. Satralizumab (Active) | (6, 13, 40) | |
| IL-8 | Monocyte, Mφ | ↑ | Inflammatory chemokine | None | (6) | |
| IL-10 | Treg, Th2, monocytes, activated B cell subsets | ↓ | Antiinflammatory | - | (6) | |
| IL-17A/C | Th17 cells, strong | ↑ | Proinflammatory | Inconclusive | (41, 42) | |
| IL-12 | Monocyte, Mφ | ↑ | Proinflammatory | Unknown | (38, 39) | |
| IL-15 | Monocyte, Mφ, DCs | ↑ | Proinflammatory | Unknown | (38) | |
| IL-19 | B cells, monocytes | ↑ | Induces IL6 and TNF expression; helps in Th2 functions | Present | (38) | |
| IL-20 | Monocyte, DCs, granulocytes | ↑ | Proinflammatory | Present | (38) | |
| IL-22 | Th17, Mφ | ↑ | Both pro- and antiinflammatory; skin inflammation | Present | (43) | |
| IL-28 A | Tregs, DCs | ↓ | Suppress proinflammatory cytokines | Present | (38) | |
| IL-35 | Tregs, B regs | ↓ | Suppress effector B and T cells | Present | (38) | |
| eotaxin | Eotaxin 1/ccl11: Produced by TNF-stimulated monocytes IFNγ-stimulated endothelial cells | ↑ | Chemoattractant for Th2 cells, eosinophils, and basophils. | Unknown | (38) | |
| APRIL | Mφ, DCs, eosinophils, and neutrophils. | ↑ | Costimulator of B and T cell proliferation | Present | (38) | |
| MMP | Mφ, neutrophils, T cells | ↑ | Wound healing | Unknown | (6) | |
| TGFα | T reg cells | ↑ | Suppress CD8 cells, | - | (6, 44) | |
| EN-RAGE | Monocytes, T cells, endothelial cells | ↑ | Activates inflammatory cascades | Unknown | (6) | |
| BDNF | T cells, B cells, monocytes | ↑ | Promote inflammation | Unknown | (6) | |
| VEGF | Mφ | ↑ | Proinflammatory | Unknown | (38) | |
| CCL19 | T cells, DCs | ↑↓ | Dual role (Pro- or antiinflammatory) | - | (6, 7) | |
| C-X-CL | Tfh cells, | ↑ | Proinflammatory | Unknown | (6, 7, 45) | |
| MIP-1(α, β)/CCL3 | Monocytes, T/B cells, DCs, NK cells | ↑ | Recruit inflammatory cells | Unknown | (6) | |
| IFN | Th1 | ↑ | Pleiotropic function; regulate Th17 cells, modulate DC antigen presentation | Not present | (23, 33, 46–48) | |
| BAFF | B cells, T cells. | ↑ | Survival and maturation of B cells | Present | (7, 49) | |
| Hmg-1 | Ubiquitous, all cells | ↑ | Promote inflammation | Unknown | (50, 51) | |
IL, interleukin; APRIL, A proliferation-inducing ligand; MMP, Matrix metalloproteinases; TGF, transforming growth factor; EN-RAGE, Extracellular newly identified receptor for advanced glycation end products binding protein; BDNF, Brain-derived neurotrophic factor. Up arrow, upregulated; down arrow, downregulated.