TABLE 1.

Publications reporting CSF and blood circulating inflammatory molecules in ALS and FTD patients.

Compartment	ALS	FTD
CNS	Increased circulating factors in CSF: cytokines and chemokines: IL-2, IL-4, IL-5, IL-7, IL-8, IL-9, IL-12, IL-15, IL-17, IFN-γ, TNF-α, eotaxin, CCL11, MIP-1α, MIP-1β, MCP-1, IP-10 (Tanaka et al., 2006; Kuhle et al., 2009; Mitchell et al., 2009; Tateishi et al., 2010; Gonzalez-Garza et al., 2018); growth factors: FGF-2, VEGF, G-CSF, GM-CSF, PDGF-BB (Tanaka et al., 2006; Mitchell et al., 2009; Tateishi et al., 2010; Furukawa et al., 2015; Guo et al., 2017) Contradictory results: increase or decrease of IL-10 (Tanaka et al., 2006; Mitchell et al., 2009)	Increased circulating cytokines in the CSF: IL-8, IL-11, IL-23, MCP-1, IP-10, Eotaxin-3, TGF-β1, YKL40 (Sjögren et al., 2004; Galimberti et al., 2006, 2008, 2015; Hu et al., 2010; Bossù et al., 2011; Teunissen et al., 2016) Decreased circulating cytokines in the CSF: IL-12, IL-15, IL-17, TNF-α, RANTES (Rentzos et al., 2006a; Hu et al., 2010; Galimberti et al., 2015) Increased inflammatory lipids in the CSF: LPC, PAF (Phan et al., 2020)
Blood	Increased circulating factors linked with extracellular matrix remodeling: MMP9, TIMP2 (Andrés-Benito et al., 2017); oxidative stress markers: GSSG, 8-OHdG, MDA (Blasco et al., 2017); circulating cytokines/chemokines: IL-1β, IL-4, IL-8, IL-12p70, IL-13, IL-15, IL-17A, IL-18, TNF-α, MIP-1α, MCP-1, eotaxin (Kuhle et al., 2009; Italiani et al., 2014; Ehrhart et al., 2015; Ngo et al., 2015; Lu et al., 2016; Blasco et al., 2017; Guo et al., 2017; Prado et al., 2018; Tortelli et al., 2020; Brodovitch et al., 2021); growth factors: G-CSF, GM-CSF, bFGF, VEGF (Guo et al., 2017) Downregulation of inflammatory cytokines chemokines CCL5, CXC5R, TGF-β2, IL-10RA (Ehrhart et al., 2015; Andrés-Benito et al., 2017), oxidative stress markers: GSH (Ehrhart et al., 2015; Blasco et al., 2017) Contradictory results: increase or decrease of IL-2, IL-5, IL-6, IL-10, IFN-γ (Ehrhart et al., 2015; Lu et al., 2016; Andrés-Benito et al., 2017; Blasco et al., 2017; Guo et al., 2017; Prado et al., 2018; Tortelli et al., 2020; Brodovitch et al., 2021)	Increased peripheral circulating cytokines IL-6, IL-8, IL-15, IL-17, CCL26, MCP-1, IP-10, TNF, FasL, TRAILR3 (Bossù et al., 2011; Miller et al., 2013; Gibbons et al., 2015) Decreased peripheral circulating cytokines IL-1α, IL-6, IL-12, IL-23, RANTES, TNF (Santos et al., 2014; Galimberti et al., 2015)

This table recapitulates circulating inflammatory molecules measured in the CSF and the blood of patients. The molecules can be secreted by several immune cell types. 8-OHdG, 8-hydroxydesoxyguanosine; bFGF, basic fibroblast growth factor; CCL5, C-C motif chemokine ligand 3; CCL11, C-C motif chemokine ligand 11; CCL26, C-C motif chemokine ligand 26; CXC5R, C-X-C motif chemokine receptor 5; FasL, Fas ligand; FGF-2, fibroblast growth factor 2; G-CSF, granulocyte-colony stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GSH, glutathione; GSSG, glutathione disulfure; IFN-γ, interferon-gamma; IL-1β, interleukin-1 beta; IL-2, interleukin-2; IL-4, interleukin-4; IL-5, interleukin-5; IL-6, interleukin-6; IL-7, interleukin-7; IL-8, interleukin-8; IL-9, interleukin-9; IL-10, interleukin-10; IL-10RA, interleukin 10 receptor subunit alpha; IL-11, inteleukin-11; IL-12, interleukin-12; IL-12p70, interleukin-12p70; IL-13, interleukin-13; IL-15, interleukin-15; IL-17, interleukin-17; IL-17A, interleukin-17A; IL-18, interleukin-18; IL-23, interleukin-23; IP-10, interferon gamma-induced protein 10; LPC, lysophosphatidylcholine; MCP-1, monocyte chemoattractant protein 1; MDA, malondialdehyde; MIP-1α, macrophage inflammatory protein-1 alpha; MIP-1β, macrophage inflammatory protein-1 beta; MMP9, matrix metallopeptidase 9; PAF, platelet-activating factor; PDGF-BB, platelet-derived growth factor-BB; RANTES, Regulated Upon Activation, Normally T-Expressed, and Presumably Secreted (or CCL5); TGF-β1, transforming growth factor beta 1; TGF-β2, transforming growth factor beta 2; TIMP2, tissue inhibitor of metalloproteinases 2; TNF-α, tumor necrosis factor alpha; TRAILR3, tumor-necrosis-factor related apoptosis inducing ligand receptor 3; VEGF, vascular endothelial growth factor; YKL-40, chitinase 3-like 1.