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.