THERAPEUTIC TARGETS FOR NON-INFECTIOUS UVEITIS BY CYTOKINE PROFILING IN AQUEOUS HUMOR SAMPLES
- Stefania Croci, Italy
Abstract
Background and Aims
Non-infectious uveitis comprises sight-threatening intraocular inflammatory conditions with unknown etiology. Corticosteroid are the mainstay of therapy. However, tailoring therapies on each individual molecular profile and developing new targeted-therapies are unmet clinical needs. We thus aimed to identify cytokines dysregulated in aqueous humor (AH) from patients with uveitis associated with Behcet’s (BD) and Vogt-Koyanagi-Harada (VKH) disease, two systemic inflammatory diseases.
Methods
Concentrations of 27 cytokines were measured in AH samples from patients with active panuveitis (n=10 BD, n=10 VKH) versus healthy controls (HC, n=10) using a multiplex immunoassay. Leukocytes in AH were counted and characterized by flow cytometry.
Results
IL-6, IP-10, G-CSF, IFNγ showed higher concentrations in AH from both BD and VKH patients while IL-2, IL-4, IL-8, IL-13, TNFα, MIP-1α, eotaxin, IL-1ra showed higher concentrations only in AH from BD patients compared with HC. GM-CSF was the sole cytokine with lower levels in AH from BD patients. No statistically significant differences were found between BD and VKH patients. The concentrations of IL-6, IL-4, IL-8, IP-10, G-CSF, IFNγ, TNFα, MIP-1α, eotaxin, IL-1ra positively correlated with the concentrations of leukocytes in AH, mainly with those of monocytes and granulocytes, suggesting that such cytokines were produced by and/or attracted and/or promoted proliferation and survival of immune cells in these types of uveitis. The AH over plasma cytokine ratios intra-individuals suggested that IL-2, IL-6, IP-10, GM-CSF were produced also intraocularly.
Conclusions
AH sampling followed by cytokine profiling can highlight which cytokines are dysregulated intraocularly in each individual, providing a rationale for tailoring treatments in patients with non-infectious uveitis.