Potential Anti-inflammatory Properties Of Leukemia Inhibitory Factor In Ocular Behcet’s Disease And VKH Syndrome

Objectives: Leukemia inhibitory factor (LIF) has pleiotropic effectsand has been shown to possess both pro-inflammatory andanti-inflammatory properties. Direct effects of LIF on CD4+T cells afterstimulations are not yet clear and whether LIF can play a role in ocularBehcet’s disease and VKH syndrome has not yet been addressed. They werehence the subjects of our experiments.Methods: Effects of LIF on CD4+T cell response were determined byflow cytometry and cell proliferation assays. Expressions of T-bet, RORγt,and Foxp3mRNA in CD4+T cells were assayed by RT-PCR.Phosphorylations of MAPK were measured by flow cytometry. Expressionof LIF mRNA in PBMCs and protein in sera from uveitis patients withVogt-Koyanagi-Harada (VKH) syndrome and Behcet’s disease (BD) wereanalyzed by RT-PCR and ELISA. Spg130in serum and cytokines in thesupernatants of CD4+T cells were measured by ELISA. Results: LIF significantly inhibited the expansion of Th17andIL17+IFN-γ+cells following anti-CD3and anti-CD28antibodiesstimulations, and decreased IL-17secretion. It also dampened the expressionof RORγt. LIF promoted ERK1/2phosphorylation transiently. LIF mRNAexpression was significantly lower in patients with active VKH and activeBD compared with healthy controls. The expression level of LIF mRNA ininactive patients ranged between the values observed in active patients andhealthy individuals. LIF protein was above the detection limit in10out of38samples from active uveitis patients,12out of28from inactive uveitispatients, compared to7out of15from controls. CD4+T cells from patientstreated with rLIF showed an attenuated IL-17secretion.Conclusion: LIF affects the response of stimulated CD4+T cells andmay thus play a role in the pathogenesis of immunological diseases likeuveitis seen in VKH and BD.