Two Studies Show IL-35 Protein’s Potential to Curb Inflammation in Autoimmune Diseases

An immune signaling protein called interleukin-35 has anti-inflammatory properties that scientists might harness to develop a therapy for multiple sclerosis and other autoimmune disorders, according to two studies.

Researchers at the National Eye Institute of the National Institutes of Health discovered that a subunit of interleukin 35, which is also known as IL-35, significantly reduced inflammation in mouse models of eye inflammation and multiple sclerosis.

Immune B-cells produce IL-35 to communicate with, and regulate the behavior of, surrounding cells. In a previous study, the research team found that the protein could inhibit inflammation in the eyes of animals with autoimmune uveitis, or inflammation of the inner layers of the eye. An autoimmune disease is one in which the immune system attacks healthy cells instead of invaders.

A drawback of trying to use a synthetic version of IL-35 as a therapy is that it’s difficult to produce because of its complex structure and it’s unstable in a solution. Natural IL-35 is composed of two subunits, IL-12p35 and Ebi3, which bind to create the full protein.

The team wondered if they could use a subunit, instead of the full protein, as an anti-inflammatory agent. Their study, “IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease,” was published in the journal Nature Communications,

They demonstrated that the IL-12p35 subunit could generate anti-inflammatory effects similar to those of the full IL-35 protein.

Giving IL-12p35 to mice with uveitis promoted the expansion of immune B-cells that counteract autoimmune responses, reversing the animals’ eye symptoms.

“These individual subunits may form a new generation of biologics that can be used to treat autoimmune and neurodegenerative diseases,” Dr. Charles Egwuagu, chief of the Molecular Immunology section at the National Eye Institute’s Laboratory of Immunology, said in a news release. He was senior author of the study.

In the second study, researchers discovered that the subunit tempered inflammation in a mouse model of multiple sclerosis. Giving the animals IL-12p35 every other day for up to 12 days promoted immune cell proliferation that inhibited inflammation in the mice’s brains and spinal cords, improving their symptoms.

The research demonstrated IL-35 and its subunit’s potential to treat nerve-inflammation disorders. The team published its findings in the journal Frontiers of Immunology. The article is titled “IL-12p35 inhibits neuroinflammation and ameliorates autoimmune encephalomyelitis.”

“We were able to recapitulate the activity of the heterodimer cytokine [IL-35] just by using one subunit, and that makes it a much more important contribution to the field of developing biologics to treat these diseases,” Egwuagu said.

The team is now looking at IL-12p35’s ability to treat other degenerative eye diseases, such as diabetic retinopathy and macular degeneration.