Adrenomedullin protects from experimental autoimmune encephalomyelitis at multiple levels

Brain Behav Immun, 2014 · DOI: 10.1016/j.bbi.2013.11.021 · Published: March 1, 2014

Simple Explanation

Adrenomedullin, a neuropeptide, was investigated for its effects on experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. The study found that adrenomedullin treatment reduced the severity and incidence of EAE. Adrenomedullin achieves this by affecting multiple stages of the disease, including reducing inflammation in the spinal cord, demyelination, and axonal damage. Furthermore, adrenomedullin promoted the generation of regulatory T cells, which help suppress the autoimmune response, and modulated dendritic cells, which play a role in antigen presentation.

Study Duration

Not specified

Participants

Female C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
Adrenomedullin treatment reduced the clinical severity and incidence of EAE, the appearance of inflammatory infiltrates in spinal cord and the subsequent demyelination and axonal damage.
2
Adrenomedullin decreased the presence/activation of encephalitogenic Th1 and Th17 cells and down-regulated several inflammatory mediators in peripheral lymphoid organs and central nervous system.
3
Adrenomedullin regulated glial activity and favored an active program of neuroprotection/regeneration.

Research Summary

This study reports that adrenomedullin provides a highly effective therapy for chronic EAE by reducing inflammatory infiltrates in the CNS and subsequent demyelination and axonal damage. Adrenomedullin treatment decreased the presence of encephalitogenic Th1 and Th17 cells in the periphery and CNS, primarily by regulating encephalitogenic sensitization in the peripheral immune compartment. Adrenomedullin promotes long-lasting antigen-specific suppressive responses through the induction of Treg cells and tolerogenic DCs and mounting an active program of neuroprotection.

Practical Implications

Therapeutic Potential

Adrenomedullin may be a therapeutic option in MS due to its multimodal action on neuropathological components.

Neuro-Immune Communication

Adrenomedullin is a key player in the bidirectional communication between the neuroendocrine and immune systems.

Clinical Translation

Adrenomedullin-based treatments have been proven safe and effective in several human pathologies, including inflammatory disorders, suggesting imminent clinical translation for MS.

Study Limitations

1
The precise mechanisms by which adrenomedullin regulates T cell responses require further investigation.
2
The role of endogenous adrenomedullin in EAE needs to be further explored using cell- and tissue-conditional knockout mice.
3
It remains to be determined whether adrenomedullin induces antigen-specific Treg cells in vivo.

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