TABLE 1.
The major role of cytokines and chemokines in ALS.
| Molecules | Secreting cells | Change in ALS | Role in the immune system | References |
| TNF-α | Macrophages, T lymphocytes, NK cells | Increased | Proinflammation: activation of immune cells | Tortarolo et al., 2017; Bougea, 2019 |
| IL-1β | Monocytes, macrophages; M1 microglia | Increased | Proinflammation: activation of immune cells | Italiani et al., 2014; Sun et al., 2022 |
| IL-6 | Immune cells, endothelial cells, myocytes | Increased/unchanged | Proinflammation: activation of immune cells | Martinez-Merino et al., 2018; Pronto-Laborinho et al., 2019; Wosiski-Kuhn et al., 2019 |
| IL-8/CXCL8 | Monocytes, endothelial cells | Increased | Proinflammation: recruitment of neutrophils, activation of glial cells | Rusconi et al., 2017 |
| IL-10 | Monocytes, T lymphocytes, and B lymphocytes; immunosuppressive microglia (M2) | Increased/increased in the early stage and decreased during disease progression | Anti-inflammation: limiting excessive production of proinflammatory cytokines, ROS. |
Batista et al., 2009; Noh et al., 2014; Strickland et al., 2020 |
| IL-13 | Th2 cells, CD4 cells, natural killer T cells, mast cells, basophils, eosinophils, and neurocytes | Increased | Controversial mechanism: proinflammation: enhancing MCP-1 expression in monocytes and macrophages; anti-inflammation: induce infiltration to the injured spinal cord and anti-inflammatory polarity of macrophages | Shi et al., 2007; Lu et al., 2016; Amo-Aparicio et al., 2021 |
| IL-17a | Th17 cells, CD8+ T cells, mast cells; astrocytes | Increased | Proinflammation | Fiala et al., 2010; Jin et al., 2021 |
| IL-33 | Multiple cells | Induced | Anti-inflammation: decreasing the proportion of CD4+ and CD8+ T cell populations, regulating mast cells function | Lin et al., 2012; Korhonen et al., 2019 |
| G-CSF | Monocytes and macrophages | Induced | Dual mechanism: inducing mobilization of bone marrow cells from bone to the peripheral, stimulating proliferation, inducing the recruitment of microglia in the damaged areas | Salamone et al., 2020 |
| CXCL13 | MNs | Increased | Anti-inflammation | Trolese et al., 2020 |
| CXCL12 | Bone marrow stromal cells | Increased | Proinflammation: development of T and B lymphocytes, influencing survival of mature Lymphocytes, microglial pathology, and permeability of CNS barriers |
Li and Ransohoff, 2008; Rabinovich-Nikitin et al., 2016 |
| CX3CL1 | MNs, microglia | Increased | Proinflammation: activation of microglia | Zhang et al., 2018 |
| CCL2 | MNs, microglia, astrocytes | Increased | Proinflammation: activation and recruitment of NK cells, T cells | Garofalo et al., 2020 |
| CCL5 | T lymphocytes, macrophages, endothelial cells | Increased | Proinflammation: proliferation and activation of T lymphocytes, monocytes | Perner et al., 2018 |
| CCL18/MIP-4 | DC | No changed | Proinflammation: attracting lymphocytes toward DC and activated macrophages, activation of microglia | Martinez-Merino et al., 2018 |
TNF-α, Tumor Necrosis Factor; IL, Interleukin; G-CSF, Recombinant Human Granulocyte-Colony Stimulating Factor; CCL, C-C Motif Ligand; CX3CL1, C-X3-C Motif Chemokine Ligand 1; CXCL, C-X-C Motif Chemokine Ligand; MIP-4, Macrophage Inflammatory Protein-4; DC, Dendritic Cell.