Researchers in Portugal Examine Role of Interleukin-17 in Uveitis

The role of interleukin-17 (IL-17) in the pathogenesis of uveitis has important implications for the diagnosis and treatment of both the noninfectious and the infectious forms of the disease, according to Maria Catarina Esteves Guedes, MD, of the Western Lisbon Hospital Center in Lisbon, Portugal. She and her team summarized this role and its implications in a recent review.

Expression of IL-17 is higher in the aqueous humor or peripheral blood of patients with noninfectious uveitis compared with that in healthy subjects. Types of uveitis studied included those associated with Behçet’s disease (BD), human leukocyte antigen-B27, and Vogt-Koyanagi-Harada disease.

Researchers also found higher expression of IL-17 in these fluids in patients with autoimmune diseases including ankylosing spondylitis, which is often associated with noninfectious uveitis. And another team of researchers showed that IL-17 levels were markers of disease activity in uveitis patients.

Furthermore, the cytokine has been implicated in the development of some forms of infectious uveitis. One study found that it was upregulated in the ocular fluid of most screened patients with toxoplasmic uveitis. These findings prompted the study’s investigators to propose that IL-17 may be a key element in the pathogenesis of autoimmune ocular inflammation after infection.

Another study found that, although patients with toxoplasmic infection have increased intraocular levels of IL-17A, patients with viral uveitis have increased expression of IL-1β and IL-10. These results led the study’s investigators to suggest using patterns of elevated cytokines in ocular fluid as specific diagnostic markers for each type of pathogen.

In addition, the pathogenic role of IL-17 found in patients with acute ocular toxoplasmosis led investigators to propose local treatment with antibodies. Such treatment of chronic noninfectious uveitis produced improvements in visual acuity and reductions in intraocular inflammation comparable to those found historically in similar patients treated with infliximab (Remicade/Janssen).

However, the SHIELD trial of the anti-IL-17 antibody secukinumab (Cosentyx/Novartis) for BD-associated uveitis did not meet its primary outcome measure. As a result, investigators stopped the INSURE and ENDURE trials of secukinumab in patients with noninfectious uveitis not associated with BD.

Some experts have argued that cessation of these trials was a premature reaction to the SHIELD results, particularly because SHIELD did find a reduction in the concomitant use of immunosuppressants and a trend toward reduced recurrence of BD uveitis. Moreover, intravenous secukinumab produced good results in a recent study of 37 patients with active noninfectious intermediate or posterior uveitis or panuveitis requiring immunosuppressants.

Other monoclonal antibodies that affect the IL-17 pathway include ustekinumab (Stelara/Janssen), which is directed at the IL-23 and IL-12 p40 subunit, and tocilizumab, which is directed against the IL-6 receptor. IL-6 is necessary for Th17 differentiation and IL-17 expression, and IL-23 has an important role in Th17 cell expansion and activation.

The US Food and Drug Administration (FDA) has approved ustekinumab for treating psoriasis, psoriatic arthritis, and Crohn’s disease. And because a similar antibody suppressed IL-17 production and improved the ocular condition of animals with experimental autoimmune uveitis, ustekinumab may provide another uveitis treatment option.

In addition, the FDA has approved tocilizumab (Actemra/Roche) for treating juvenile idiopathic arthritis (JIA), a disease often associated with uveitis. In one study, tocilizumab was shown to induce remission in most patients with severe, refractory, JIA-associated uveitis after six months of therapy. Tocilizumab is also being evaluated as a treatment for other forms of noninfectious uveitis.

The review, “Roles of interleukin-17 in uveitis,” was published online in November 2016 in the Indian Journal of Ophthalmology.

Related Coverage:

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Study: IL-1 Inhibitors Controlled Behçet’s Disease-Related Uveitis

Tocilizumab Effective for Uveitis in Juvenile Idiopathic Arthritis