NOVEL drugs for the treatment of rheumatoid arthritis could earn a place in the medicine cabinet following the results of a study from researchers at the Karolinska Institutet in Solna, Sweden. The study demonstrated the actions of endogenous proteins, involved in allergic and parasitic infections, in preventing autoimmune reactions which provoke joint inflammation.
The researchers identified that IL-4 and IL-13 play a vital role in preventing the attack of the immune system on the body and, despite studies which have previously indicated the association of these proteins with arthritis on experimental models, their precise action had not been evidenced.
Specific immune-cell genes were modified using the CRISPR method and their effect on cell behaviour was monitored. The principal investigator of the study, Dr Fredrik Wermeling, commented on the highly commended CRISPR system: “The results we obtained using CRISPR were key to quickly understanding how the system under study is regulated. I have high hopes that the experimental use of CRISPR will be hugely important to our understanding of how immune-cell behaviour is regulated, and that this can guide us in the development of new efficacious drugs.”
Neutrophils are influenced by the secretion of IL-4 and IL-13 following infection; they are the immune cells most commonly found in the actively inflamed joints of patients with rheumatoid arthritis, associated with secreting various nonspecific irritants in the tissue. In this study, IL-4 and IL-13 were shown to prevent the migration of neutrophils to the site of joint inflammation. These proteins also acted by stimulating increased expression of neutrophil surface receptors, causing further inhibitory effects on the inflammation. Dr Wermeling spoke optimistically of the endeavours of the researchers: “We will continue to study these mechanisms and hope that our work can contribute to the development of treatments for rheumatoid arthritis”.