Researchers Conduct Review of Interleukin-17 Controversies Across Medical Fields

Researchers outlined a comprehensive review of the common mechanisms through which interleukin-17 (IL-17) is considered a molecular target for developing novel biological therapies in several different fields of medicine, according to a report published by Autoimmunity Reviews.

IL-17 cytokines are made up of 6 proteins (IL-17A to IL-17F) as well as 5 receptors (IL-17RA to IL-17RE). The researchers explained that while IL-17A and IL-17F are made of several types of immune cells, the other proteins are produced by epithelial cells and receptors are distributed among common cells types.

“Targeted manipulation of the immune system in animal models has led to insights into disease pathogenesis, but is contribution to formulate clinical and therapeutic concepts in humans has been much more limited,” explained the authors. “Thus, in experimental animal models of chronic inflammatory diseases such as posterior uveitis, psoriasis, inflammatory bowel disease, multiple sclerosis, collagen-induced arthritis and ankylosing spondylitis, IL-17A appeared to be a crucial pathogenic molecule.”

The researchers outlined the research and controversies of IL-17 in a variety of medical fields, with current controversies existing in dermatology. Previous research suggests IL-17 is present in the pathophysiology of a large number of inflammatory dermatoses, however, the potential activity of IL17A inhibitors and their long-term efficacy remains to be a challenge for scientists.

In hepatology, the report suggests that the blockage of IL-17 axis must show clinical benefit in non-alcoholic fatty liver disease. As for cardiology, the role of IL-17A in cardiovascular risk has been demonstrated in studies with cell cultures and vivo studies, however, additional studies are needed to determine the therapeutic effect of blocking IL-17A in patients with chronic inflammatory diseases at risk of negative cardiovascular events.

“A relevant involvement of IL-17A has been postulated in the development and maintenance of arterial hypertension, endothelial dysfunction, myocardiocyte apoptosis and in the extent of myocardial infarction in ischemia/reperfusion models,” researchers said. “Regarding IL-17A relationship with atherosclerosis, there are controversial aspects determined by its dual proatherogenic and anti-atherogenic action, which in clinical models of chronic systemic inflammation could shift towards a preponderant proatherogenic effect based on its synergistic action with TNTα.”

The controversies outlined by researchers suggest starting points for future studies in each field.

Reference

Ruiz de Morales JMG, Puig L, Dauden E, et al. Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies. [published online November 15, 2019]. Autoimmunity Reviews. doi: 10.1016/j.autrev.2019.102429.