Neurodegenerative diseases are characterized by the progressive loss of structure or function of neurons, including the death of neurons. The most commonly studied neurodegenerative diseases are Multiple sclerosis (MS), Alzheimer’s Disease (AD), and Parkinson’s disease (PD). Cytokines are small proteins involved in inter-cellular signalling pathways. Numerous cytokine responses have been implicated in neurodegenerative diseases.
In numerous studies, the following cytokines have been implicated in the above three neurodegenerative diseases. These studies were performed detecting cytokines in either cerebrospinal fluid (CSF) or serum of patients. Multiplexing is especially useful when measuring limited sample types such as CSF.
- IL-1beta is a proinflammatory cytokine made by cells including monocytes, tissue macrophages and dendritic cells.
- IL-2 is an immunoregulatory lymphokine produced by T-cells in response to mitogenic or antigenic stimulation.
- IL-4 regulates diverse T and B cell responses such as cell proliferation, survival and gene expression
- IL-6 plays an important role in host defense by regulating immune and inflammatory responses. It is made by T-cells, monocytes, fibroblasts, endothelial cells and keratinocytes.
- IL-10 is an immunosuppressive cytokine made by macrophages, monocytes, T cells, B cells and keratinocytes. It inhibits expressions of Proinflammatory cytokines such as IL-1.
- IL-12 is a strong regulator of cell-mediated immune response. It often induces IFN-gamma production by natural killer (NK) and T cells.
- TNF-alpha is a Proinflammatory cytokine secreted by adipocytes, activated monocytes, macrophages, B cells, T cells and fibroblasts.
- TGF-beta regulates cell proliferation, growth, differentiation, and motility.
- MCP-1 (Monocyte Chemoattractant Protein) chemoattracts and activates monocytes, activated T cells, basophils, NK cells and immature dendritic cells.
- MIP-1 (Macrophage Infllammatory Protein-1) participates in the host response to invading bacterial, viral, parasitic and fungal pathogens by regulating the trafficking and activation of subgroups of inflammatory cells, such as macrophages, lymphocytes, and NK cells.
- IFN-gamma (Interferon-gamma) regulates the antigen-specific phases of the immune response and is highly conserved among animal species.
The following table summarizes the responses of the eleven cytokines in each of the three disease states. Each cytokine can have increase (+), decrease(-), or a increase or decrease (±) in expression.
| Cytokines in 3 Disease States | |||
|---|---|---|---|
| Multiple Sclerosis | Alzheimer’s Disease | Parkinson’s Disease | |
| IL-1beta | + | + | + |
| IL-2 | – | + | |
| IL-4 | ± | – | + |
| IL-6 | + | + | + |
| IL-10 | – | ||
| IL-12 | + | ||
| TNF-alpha | + | + | + |
| TGF-beta | – | + | |
| MCP-1 | + | ||
| MIP-1 | + | ||
| IFN-gamma | + | ||
The above chart was adapted from Malekzadeh et al. 2012, “Challenges in multi-plex and mono-plex platforms for the discovery of inflammatory profiles in neurodegenerative diseases, a review of neurodegenerative biomarker studies.” This review clearly demonstrates that multiple biomarkers must be studied in order to gain a thorough understanding of disease processes.
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