Abstract
Purpose: :
To characterize the cytokine pattern in aqueous humor (AH) of patients with chronic granulomatous anterior uveitis where we previously showed distinct T cell phenotypes according to clinical presentation.
Methods: :
Forty one patients were included. Twenty of them had infectious granulomatous anterior uveitis (fifteen with ocular toxoplasmosis, and five with herpetic uveitis). Seven patients presented with Fuchs Heterochromic Cyclitis (FHC), displaying mixed rounded keratic precipitates and typical stellar ones. Four patients had biopsy–proved sarcoidosis. Finally, ten patients were classified as idiopathic granulomatous uveitis, because all usual etiological investigations returned negative. Aqueous humor results of these 41 patients were compared with twelve control samples, obtained during non–inflammatory diseases surgery.
As AH amount was limited for each patient, we used a cytokine multiplex fluorescent beads technique to measure simultaneoulsly several cytokines in the same sample.
Seven cytokines (i.e. IL–2, IL–4, IL–5, IL–6, IL–10, TNF–α, IFN–γ) were analyzed, using Human Th1/Th2 Cytokine Bead Assays.
Results: :
IL–6 was significantly increased in all granulomatous uveitis, except in FHC, compared to controls (p=0.011). Within granulomatous uveitis, IFN–γ was strongly and significantly increased in infectious uveitis, especially in ocular toxoplasmosis (p=0.009). Interestingly, these infectious uveitis showed also strong levels of immunomodulatory cytokine IL–10 compared to non infectious uveitis and controls (p=0.021). In FHC, only IL–2 and IL–10 were increased compared to controls (p=0.002 and 0.019, respectively).
Conclusions: :
Our results showed that, oppositely to FHC, strong granulomatous intraocular inflammation was associated with high levels of IL–6, a cytokine which is believed to play a pivotal role in experimental autoimmune uveitis. Furthermore, increased IFN–γ levels were found in infectious granulomatous uveitis, possibly underlying specific response to intracellular pathogens (i–e Toxoplasma Gondii and Herpes viruses). We also measured high levels of IL–10 in ocular toxoplasmosis and herpetic uveitis, a well known immunomodulatory cytokine which may witness a regulatory process during these uveitis. As previously expected by studying ocular T cell phenotype, these data suggest that distinct etiologies may lead to distinct clinical presentations of granulomatous anterior uveitis and provide new evidence for the implication of various modalities of the immune response.
Keywords: uveitis-clinical/animal model • cytokines/chemokines • immunomodulation/immunoregulation