Adipokines as Immune Cell Modulators in Multiple Sclerosis
Abstract
:1. Introduction
2. MS Pathophysiology, Therapies, and Risk Factors
2.1. Pathophysiology
2.2. Disease-Modifying Treatments
2.3. Obesity as Risk Factor for MS
3. Adipokines, Inflammation, and MS
3.1. Adiponectin
3.2. Leptin
3.3. Resistin
3.4. Chemerin
3.5. Visfatin
3.6. Apelin
3.7. Confounding Factors
4. Adipokines as Therapeutic Target for MS—Evidence from Pre-Clinical Studies
4.1. Adiponectin
4.2. Leptin
4.3. Resistin
4.4. Chemerin
4.5. Visfatin
4.6. Apelin
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Adipokine | Primary Production Site (s) | Target Receptor (s) | Levels in Circulation | Role in Immunity | Changes in Circulating Levels in MS |
---|---|---|---|---|---|
Adiponectin | Adipocytes | AdipoR1 and 2 | 2.5–22 µg/mL [127] |
| ↑ early-onset RRMS females versus control [46] ↑ during remission [45] ↑ after IFN-β therapy [49] ↑ treatment-naïve patients, correlated with increased disability and progression [50] ↑ CSF, predicted worse prognosis and higher EDSS [52,53] newly diagnosed, treatment-naive patients ↓ after BMI adjustment [29] between CIS and other MS types [85] ↓ female MS versus control [48] ↓ RRMS females in relapse phase versus control [44] ↓ in patients with optic neuritis as first clinical episode [51] |
Leptin | Adipocytes | LepR/OB-R | 5–50 ng/mL [127] |
| Levels: ↑ in MS patients versus control [62,64,70] ↑ in MS patients in relapse phase versus control [44,47,66,71] ↑ CSF in relapse RRMS versus control [66] ↑ in MS patients in remission phase versus control [51,72] between CIS and other MS types [85] in MS patients in relapse phase versus control [67] in MS patients in remission phase versus control [53,63,65,67,68,69,73] CSF in MS patients in remission phase versus control [53] ↓ in MS patients in relapse phase versus control [63,72] Correlations: ↑ plasma with EDSS in RRMS [75] ↑ plasma with EDSS in SPMS/PPMS [62,76] ↑ plasma with less T-reg cells [47,64,66] ↑ plasma correlated with TNF-α, IL-1β, CRP [64] no correlation with EDSS scores in RRMS patients [49,69,73,74] |
Resistin | PBMC, adipocytes | CAP1, TLR4 | 38.78 ± 7.9 ng/mL [128] |
| ↑ plasma, correlated with pro-inflammatory cytokines and EDSS between CIS and other MS types [85] |
Chemerin | Adipocytes, hepatocytes | CMKLR1, GPR1, CCRL2 | 62.1 ± 19.2 ng/mL [129] |
| between MS and control [97,98] |
Visfatin | Adipocytes, macrophages, endothelial cells | InsR, TLR4 | 11.0 ± 2.0 ng/mL [130] |
| ↑ RRMS compared to PPMS and SPMS patients, positive correlation with TNF-α and IL-1β [64] ↑ newly diagnosed, treatment-naive patients <-> after BMI adjustment [29] |
Apelin | Adipocytes | APLNR | 205 ± 108 pg/mL [130] |
| ↑ RRMS patients compared to controls, no correlations with EDSS and disease duration [118] ↓ RRMS females less than 1 year after onset, levels correlated positively with both EDSS and number of relapses [46] |
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Rijnsburger, M.; Djuric, N.; Mulder, I.A.; de Vries, H.E. Adipokines as Immune Cell Modulators in Multiple Sclerosis. Int. J. Mol. Sci. 2021, 22, 10845. https://doi.org/10.3390/ijms221910845
Rijnsburger M, Djuric N, Mulder IA, de Vries HE. Adipokines as Immune Cell Modulators in Multiple Sclerosis. International Journal of Molecular Sciences. 2021; 22(19):10845. https://doi.org/10.3390/ijms221910845
Chicago/Turabian StyleRijnsburger, Merel, Niek Djuric, Inge A. Mulder, and Helga E. de Vries. 2021. "Adipokines as Immune Cell Modulators in Multiple Sclerosis" International Journal of Molecular Sciences 22, no. 19: 10845. https://doi.org/10.3390/ijms221910845