Aqueous cytokine and chemokine analysis in uveitis associated with tuberculosis

PURPOSE: The aim of this study was to study the aqueous cytokine and chemokine composition in patients with uveitis associated with tuberculosis (TAU). METHODS: We present a prospective case series of consecutive new patients with active uveitis presenting at a single tertiary center (January 1, 2008-January 1, 2010). Patients with no ocular pathology other than cataracts were enrolled as non-inflammatory controls. Aqueous samples were taken from all study subjects and analyzed using a magnetic color-bead-based multiplex assay for cytokine and chemokine concentrations. RESULTS: Twenty-five eyes of 25 patients with active uveitis with suspected tuberculosis (TB) and 23 non-inflammatory controls were enrolled. Ten patients tested positive on a tuberculin skin test and interferon-gamma release assay; all ten patients responded to anti-TB treatment with no recurrences (TAU). The remaining 15 eyes were negative for the above tests and had no other underlying causes for uveitis found on clinical evaluation and investigations; therefore, they were classified as “idiopathic uveitis” (IU). The TAU group showed significantly higher levels of interleukin-6 (IL-6; p=0.047), interleukin-8 (CXCL8; p=0.001), monokine induced by interferon-gamma (CXCL9; p=0.001), and interferon-gamma-induced protein 10 (IP-10 or CXCL10; p=0.002), compared to the controls. The IU group showed significantly higher levels of IL-6 (p=0.008), monocyte chemotactic protein-1 (CCL2; p=0.036), CXCL8 (p=0.001), and IL-9 (p=0.045), and significantly lower levels of IL-2 (p=0.011), IL-12 (p=0.001), and tumor necrosis factor (TNF)-α (p=0.001), compared to the controls. Heat map analysis revealed significant differences in aqueous cytokine and chemokine concentrations among the TAU patients, the IU patients, and the controls. CONCLUSIONS: In our study population, aqueous cytokine and chemokine analyses suggest that subjects with uveitis associated with TB who respond to anti-TB therapy do not have an active ocular tuberculous infection, but rather an autoimmune-related ocular inflammation that may be triggered by TB.