Evobrutinib’s Effects on Macrophages Could Be Beneficial for SLE Treatment, Study Suggests

Evobrutinib’s Effects on Macrophages Could Be Beneficial for SLE Treatment, Study Suggests
This post was originally published on this site

evobrutinib, macrophages

The investigational compound evobrutinib acts on the immune system by promoting anti-inflammatory behavior of macrophages — immune cells that engulf and digest pathogens — and the death of pro-inflammatory ones, a study reports.

This suggests benefits in systemic lupus erythematosus (SLE) and rheumatoid arthritis besides the suppression of B-cells.

The research, “Inhibition of Bruton’s Tyrosine Kinase (BTK) Prevents Inflammatory Macrophage Differentiation: A Potential Role in RA and SLE,” was presented at the recent 2018 American College of Rheumatology/Association for Rheumatology Health Professionals Annual Meeting in Chicago.

Bruton’s tyrosine kinase (BTK) was initially characterized as a mediator of B-cell receptor signaling in adaptive immunity, which is activated by pathogens and uses an immunological memory to respond appropriately.

However, accumulating evidence has shown that BTK also acts in cells of the innate immune system, such as macrophages and their precursors, monocytes. These cells may have pro-inflammatory and anti-inflammatory effects, playing a key role in both the exacerbation and control of autoimmune diseases.

Evobrutinib, a BTK inhibitor developed by Merck KGaA, suppresses B-cell responses and prevents innate immune activation via the Fc receptor. Preclinical studies suggested that evobrutinib may be effective in SLE and rheumatoid arthritis.

A team of researchers set out to study the impact of BTK inhibition with evobrutinib on the differentiation and activation of macrophages.

For this purpose, the investigators isolated monocytes from the peripheral blood of healthy volunteers and treated them with GM-CSF, a factor that usually makes monocytes grow into pro-inflammatory (M1) macrophages.

However, the results showed that BTK activation was mediated by the GM-CSF receptor, and treatment with evobrutinib caused M1 macrophages to die.

To determine if monocytes were converting into pro-inflammatory or anti-inflammatory (M2) macrophages, the researchers examined a range of molecules specific to each macrophage subtype.

They found that, after treatment with evobrutinib, monocytes were producing significantly less of the pro-inflammatory molecules interleukin (IL)-1 beta and TNF-alpha, but more of the IL-10 anti-inflammatory protein, suggesting that these cells were turning into M2 macrophages.

M2 macrophages also worked better after treatment, clearing death cells in a more efficient way than prior to treatment. 

“Our findings show that BTK inhibition hinders M1 macrophage differentiation and skews monocytes towards an anti-inflammatory M2 phenotype, while enhancing apoptotic cell uptake by M2 cells,” the scientists wrote.

According to the team, these findings suggest that evobrutinib could have additional benefits in autoimmune diseases such as SLE and rheumatoid arthritis, by targeting both B-cells and myeloid cells, which include monocytes and macrophages.

Of note, three of the study’s authors are affiliated with Merck KGaA, while another is affiliated with EMD Serono (Merck KgaA in the U.S. and Canada).

The post Evobrutinib’s Effects on Macrophages Could Be Beneficial for SLE Treatment, Study Suggests appeared first on Lupus News Today.

Chris Comish serves as the Publisher of the website, and is responsible for directing the editorial focus as well as putting the finishing touches on many featured articles.