Ingested (oral) anti-IL-12/23 inhibits EAE.

Area of Science:

• Immunology and Neuroscience
• Autoimmune Disease Research
• Drug Efficacy Studies

Background:

• Interleukin-12/23 (IL-12/23) pathway is implicated in autoimmune conditions like psoriasis.
• Targeting IL-12/23 with antibodies shows therapeutic potential in inflammatory diseases.

Purpose of the Study:

• To investigate the anti-inflammatory effects of orally administered ustekinumab (UTZ) in a mouse model of experimental autoimmune encephalomyelitis (EAE).
• To assess if oral UTZ can replicate the therapeutic benefits seen with other administration routes for autoimmune conditions.

Main Methods:

• Mice with established MOG peptide-induced EAE were orally administered isotype IgG control or ustekinumab (UTZ).
• Immune cells (splenocytes, T cells, monocytes) from UTZ-fed or control-fed mice were adoptively transferred to recipient mice with ongoing EAE.
• Disease progression, central nervous system (CNS) inflammation, and cytokine profiles were analyzed in both actively treated and recipient mice.

Main Results:

• Oral administration of UTZ significantly inhibited EAE progression and reduced inflammation in treated mice.
• Adoptive transfer of immune cells from UTZ-fed donors conferred protection against EAE in recipient mice.
• UTZ treatment decreased pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, IL-17, TNF-α) and increased anti-inflammatory cytokines (IL-4, IL-10, IL-13).

Conclusions:

• Orally administered ustekinumab (UTZ) demonstrates efficacy in inhibiting experimental autoimmune encephalomyelitis (EAE).
• UTZ treatment reduces central nervous system inflammation and modulates pro-inflammatory and anti-inflammatory cytokine profiles.
• This study supports the potential of oral UTZ as a therapeutic strategy for autoimmune CNS inflammatory diseases.