Complete Freund's adjuvant as a confounding factor in multiple sclerosis research.

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Complete Freund's adjuvant (CFA) is a standard adjuvant for inducing experimental autoimmune encephalomyelitis (EAE), a key animal model for multiple sclerosis (MS).
• CFA itself triggers glial activation, neuroinflammation, and pain, independent of the targeted autoimmune response.
• The presence of Mycobacteria in CFA elicits an immune response to bacterial antigens, confounding studies focused on central nervous system autoimmunity.

Purpose of the Study:

• To detail the confounding effects of CFA in EAE models of MS.
• To introduce and advocate for the use of CFA-free EAE variants.
• To highlight CFA-free EAE as superior tools for MS research.

Main Methods:

• Review of existing literature on CFA effects in EAE.
• Description of methodologies for inducing CFA-free EAE variants.
• Comparative analysis of EAE outcomes with and without CFA.

Main Results:

• CFA induces significant glial activation, neuroinflammation, and pain, complicating the interpretation of EAE studies.
• Immune responses to CFA's bacterial components interfere with the specific study of CNS autoimmunity.
• CFA-free EAE variants successfully model autoimmune pathogenesis without confounding factors.

Conclusions:

• CFA is a significant confounding factor in EAE models used for multiple sclerosis research.
• CFA-free EAE variants provide a more accurate and reliable platform for studying MS pathogenesis.
• Adopting CFA-free EAE models will enhance the development of effective therapeutic strategies for multiple sclerosis.