Cytokines, chemokines and growth factors profile in human aqueous humor in idiopathic uveitis

Abstract

To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.

Perspectives of Therapeutic Drug Monitoring of Biological Agents in Non-Infectious Uveitis Treatment: A Review

“…A better understanding of ocular inflammation pathways has led to the emergence of biological therapies for the treatment of NIU [ 3 , 23 ] that aim to overcome the 30% failure rate obtained under classical immunosuppressive treatment [ 24 ]. Different cytokines such as TNFα, IL-6, IL-17, or IL-23 play a key role in NIU inflammatory process [ 25 ], therefore becoming very attractive as potential therapeutic targets. Bearing this in mind, randomized prospective studies have been developed in the last years to evaluate the treatment efficacy of biological drugs in NIU [ 6 , 7 , 26 ].…”

“…The presence of inflammation can alter the biodistribution coefficients at the tissue level. In fact, patients with uveitis experience an increase in vascular permeability due to the release of inflammatory mediators, such as TNFα, IL-6, IL-8, IL-17, or IL-23 [ 25 , 111 , 112 ]. This increase in vascular permeability has an impact on the integrity of the ocular barriers, which may play an important role in the penetration of high molecular weight drugs such as mAb in tissues with limited access like the eye [ 113 ].…”

Analysis of risk factors associated with secondary open-angle glaucoma in Posner-Schlossman syndrome: A retrospective case-control study

“…Aqueous humor is the most commonly used intraocular fluid for testing ( 5 – 9 ). With the development of precision medicine techniques, intraocular fluid testing has been widely used in the treatment of infectious eye diseases such as acute retinal necrosis, ocular toxoplasmosis, various types of uveitis, and other infectious eye diseases, which provides an important basis for clinicians to make accurate judgments and provide targeted treatment ( 10 – 12 ). Although there have been studies on intraocular fluid testing in patients with PSS and OAG ( 13 – 15 ), most have been limited to the correlation between intraocular fluid composition and the disease itself, and there have been no studies evaluating risk factors associated with OAG secondary to PSS.…”

Features of hemodynamic and immunological parameters in patients with recurrent uveitis complicated by hypertension, Fuchs heterochromic uveitis and Posner-Schlossman syndrome

“…Recurrent anterior uveitis of unknown etiology (or idiopathic uveitis) is the most common form of uveitis [ 2 , 3 ]. This nosological form is registered in 36% of cases [ 4 ]. One of the most serious vision-threatening consequences of this condition is secondary glaucoma, which has an incidence of 5% to 24%.…”

“…Experts note that we know little about the immune mechanisms involved in uveitis and, particularly, in idiopathic form [ 4 , 23 ]. Considering the complex pathogenetic mechanism of uveitis, it is important to study the interaction of the immune and vascular systems, as well as prevention of irreversible morphological complications.…”