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Analysis of inflammatory mediators in the vitreous humor of eyes with pan-uveitis according to aetiological classification.

ABSTRACT: Treatment of uveitis is complicated because of its multiple aetiologies and elevation of various inflammatory mediators. To determine the mediators that are elevated in the vitreous humor according to the aetiology of the uveitis, we examined the concentrations of 21 inflammatory cytokines, 7 chemokines, and 5 colony-stimulating/growth factors in vitreous samples from 57 eyes with uveitis associated with intraocular lymphoma (IOL, n?=?13), sarcoidosis (n?=?15), acute retinal necrosis (ARN, n?=?13), or bacterial endophthalmitis (BE, n?=?16). Samples from eyes with idiopathic epiretinal membrane (n?=?15), which is not associated with uveitis, were examined as controls. Heat map analysis demonstrated that the patterns of inflammatory mediators in the vitreous humor in eyes with uveitis were disease-specific. Pairwise comparisons between the 5 diseases showed specific elevation of interferon-?2 in ARN and interleukin (IL)-6, IL-17A, and granulocyte-colony stimulating factor in BE. Pairwise comparisons between IOL, ARN, and BE revealed that levels of IL-10 in IOL, RANTES (regulated on activation, normal T cell expressed and secreted) in ARN, and IL-22 in BE were significantly higher than those in the other 2 types of uveitis. These mediators are likely to be involved in the immunopathology of specific types of uveitis and may be useful biomarkers.

SUBMITTER: Fukunaga H

PROVIDER: S-EPMC7026072 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Analysis of inflammatory mediators in the vitreous humor of eyes with pan-uveitis according to aetiological classification.

Fukunaga Hisako H Kaburaki Toshikatsu T Shirahama Shintaro S Tanaka Rie R Murata Hiroshi H Sato Tomohito T Takeuchi Masaru M Tozawa Hideto H Urade Yoshihiro Y Katsura Mari M Kobayashi Mika M Wada Youichiro Y Soga Hirotsugu H Kawashima Hidetoshi H Kohro Takahide T Aihara Makoto M

Scientific reports 20200217 1

Treatment of uveitis is complicated because of its multiple aetiologies and elevation of various inflammatory mediators. To determine the mediators that are elevated in the vitreous humor according to the aetiology of the uveitis, we examined the concentrations of 21 inflammatory cytokines, 7 chemokines, and 5 colony-stimulating/growth factors in vitreous samples from 57 eyes with uveitis associated with intraocular lymphoma (IOL, n = 13), sarcoidosis (n = 15), acute retinal necrosis (ARN, n = 1 ...[more]

PMID: 32066796

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Project description:Non-infectious uveitis are intraocular inflammatory conditions caused by dysregulated activation of the immune response without any detectable infectious agents. The aim of this study was to explore potential markers and therapeutic targets for two distinct types of non-infectious uveitis associated with Behçet's disease (BD) and Vogt Koyanagi Harada (VKH) disease. Concentrations of 27 cytokines were investigated in aqueous humor (AH) samples from patients with active uveitis vs. healthy controls (HC) (n = 10 patients with BD-associated uveitis; n = 10 patients with VKH-associated uveitis; n = 10 HC) using the Bio-Plex ProTM human cytokine group I panel. Additionally, leukocytes in AH samples were counted with hemocytometers and characterized by flow cytometry. Eleven cytokines were differentially expressed between patients with uveitis and HC with a median concentration greater than 10 pg/ml. IL-6, IP-10, G-CSF, and IFN? showed higher concentrations in AH samples from both BD and VKH patients while IL-2, IL-8, IL-13, TNF?, eotaxin, IL-1ra showed statistically significant higher concentrations only in AH samples from BD patients. GM-CSF was the sole cytokine with an opposite profile showing decreased levels in AH samples from BD patients. IL-1ra and IL-6 were detected at higher frequencies in AH samples from BD and VKH patients compared with those from HC while IFN? and TNF? were not detected in HC. The concentrations of IL-6, IL-8, IP-10, G-CSF, IFN?, TNF?, eotaxin, IL-1ra positively correlated with the concentrations of leukocytes in AH, suggesting that such cytokines can be produced by immune cells and/or attract and/or promote proliferation and survival of immune cells in these types of uveitis. The correlation matrix of cytokine concentrations in AH samples revealed that IFN?, TNF?, eotaxin, IL-6, G-CSF highly correlated each other. The ratios of cytokine concentrations between AH and plasma intra-individuals showed that IL-2, IL-6, IP-10, GM-CSF were increased intraocularly. In conclusion, AH sampling followed by multiplex analysis of cytokines should be fostered in non-infectious uveitis to identify cytokines dysregulated intraocularly in each individual laying the groundwork for precision medicine.

Dataset Information

Analysis of inflammatory mediators in the vitreous humor of eyes with pan-uveitis according to aetiological classification.

Publications

Analysis of inflammatory mediators in the vitreous humor of eyes with pan-uveitis according to aetiological classification.

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