Il-17a As An Effective Target Of Anti-inflammatory And Anti-parasitic Treatment In Toxoplasmic Uveitis

Abstract

Purpose: : Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. Taking into account the opposing needs of limiting parasite multiplication and minimizing tissue destruction, the immune imbalance implies especially Th17 and T regulatory (Treg) cells.

Methods: : In a prospective clinical study of acute ocular toxoplasmosis (OT), we evaluated the cytokine pattern in aqueous humors of 10 affected patients. To further study the immunological mechanisms, we evaluated the intraocular inflammation, the parasite load and the immunological response characterized on mRNA and protein level in a mouse model. To evaluate the role of IL-17A, anti IL-17A monoclonal antibodies (mAbs) was administered concomitantly with the parasite.

Results: : We observed severe ocular inflammation and cytokine patterns comparable to human cases, including IL-17A production. Neutralizing IL-17A decreased intraocular inflammation and parasite load in mice. Detailed studies revealed upregulation of Treg and Th1 pathways. When IFN-γ was neutralized concomitantly, the initial parasite multiplication rate was partially restored.

Conclusions: : Local IL-17A production plays a central role in pathology of OT. The balance of Th17 and Th1 responses (especially IFN-γ) is crucial for the outcome of infection. These data open new in vivo therapeutic approaches by repressing inflammatory pathways using intravitreal injection of IL-17A mAbs.

Keywords: uveitis-clinical/animal model • toxoplasmosis • inflammation