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IL‐17A as a possible target of anti‐inflammatory and anti‐parasitic treatment in toxoplasmic uveitis
Author(s) -
SAUER A,
PFAFF A,
CREUZOTGARCHER C,
DALLE F,
CHIQUET C,
PELLOUX H,
SPEEGSCHATZ C,
CANDOLFI E,
BOURCIER T
Publication year - 2012
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2012.2843.x
Subject(s) - uveitis , toxoplasmosis , immunology , inflammation , cytokine , medicine , immune system , monoclonal antibody , toxoplasma gondii , interleukin 17 , parasite hosting , antibody , world wide web , computer science
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 multicenter prospective clinical study of intraocular inflammation (PHRC 3964), we evaluated the cytokine pattern in aqueous humors of 10 T. gondii infected patients. To determine the immunological mechanisms, we evaluated intraocular inflammation, parasite load, and immunological responses using mRNA and protein levels in a mouse model. Anti‐IL‐17A monoclonal antibodies (mAbs) were administered with the parasite in order to evaluate the role of IL‐17A. 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. Conclusion Local IL‐17A production by resident cells plays a central role in the pathology of OT. The balance between Th17 and Th1 responses (especially IFN‐γ) is crucial for the outcome of infection. This data reveals new in vivo therapeutic approaches by repressing inflammatory pathways using intravitreal injection of IL‐17A mAbs.