Ingested (oral) alpha-MSH inhibits acute EAE
Staley A Brod1, Zachary M Hood
1Department of Neurology, University of Texas-Houston, Health Science Center, 6431 Fannin St, Houston, TX 77030, United States. staley.a.brod@uth.tmc.edu
Abstract:
Ingested type I IFN and SIRS peptide administered orally inhibit EAE. We examined whether another immunoactive protein, tridecapeptide alpha-MSH, would have similar anti-inflammatory effects in EAE after oral administration. B6 mice were immunized with MOG peptide 35-55 and gavaged with 0.1 ml of control saline or alpha-MSH peptide starting on day -7 preceding active immunization, and continuing through day +14 post-immunization. Alpha-MSH peptide delayed disease onset and decreased inflammatory foci. CNS lymphocytes showed decreases in Th1-like encephalitogenic cytokines IL-2 and IL12p70 in the alpha-MSH fed group compared to the mock fed group. For Th2-like counter-regulatory cytokines, there were increases in peripheral SDF-1 levels comparing alpha-MSH fed vs mock fed groups. There were decreases of chemokines MIP-1-alpha and MIP-1-gamma in the CNS comparing alpha-MSH fed mice vs mock fed mice. Ingested (orally administered) alpha-MSH peptide can reduce clinical disease and inhibit CNS inflammation by decreasing migration of antigen driven CNS Th1 cells into the target organ.
Insights
Oral administration of alpha-melanocyte-stimulating hormone (α-MSH) peptide effectively reduced inflammation and delayed disease onset in experimental autoimmune encephalomyelitis (EAE). This immunoactive protein shows potential for treating neuroinflammatory conditions.
Area of Science:
- Neuroimmunology
- Inflammation Research
- Autoimmune Diseases
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis.
- Oral administration of certain peptides, like type I IFN and SIRS, can inhibit EAE.
- The immunoactive protein alpha-melanocyte-stimulating hormone (α-MSH) has anti-inflammatory properties.
Purpose of the Study:
- To investigate the anti-inflammatory effects of orally administered α-MSH peptide in a mouse model of EAE.
- To determine if α-MSH can modulate immune responses and cytokine profiles in the central nervous system (CNS) and periphery.
Main Methods:
- C57BL/6 (B6) mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55.
- Mice were orally gavaged with either α-MSH peptide or control saline from 7 days before immunization until 14 days after.
- Clinical disease progression, inflammatory foci in the CNS, and cytokine/chemokine levels (IL-2, IL12p70, SDF-1, MIP-1α, MIP-1γ) were analyzed.
Main Results:
- Oral α-MSH peptide administration significantly delayed EAE onset and reduced inflammatory foci in the CNS.
- CNS lymphocytes showed decreased levels of Th1-like encephalitogenic cytokines (IL-2, IL12p70) in the α-MSH group.
- Peripheral SDF-1 levels increased, while CNS chemokines MIP-1α and MIP-1γ decreased in α-MSH treated mice compared to controls.
Conclusions:
- Ingested α-MSH peptide demonstrates significant anti-inflammatory effects in EAE.
- Oral α-MSH inhibits CNS inflammation by reducing the migration of antigen-driven Th1 cells.
- α-MSH peptide is a potential therapeutic agent for neuroinflammatory diseases.
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