FHC and IAU are two forms of anterior uveitis which are localized to the eyes with no evidence of systemic involvement. However, FHC has distinct clinical features and differs from IAU in that the inflammation is low grade, steroid non-responsive, and has a less aggressive clinical course. To try to dissect the mechanism for this difference the phenotypes of the cells in the AH and blood (PB) and the cytokines present in the AH in patients with FHC and IAU were compared. Three-colour flow cytometry was performed on the cells isolated from the AH and PB. Percentage of cells bearing the following markers were determined: CD3, CD4, CD8, CD4/CD25, CD8/CD25, CD19 and CD14. The cytokines IL-4, IL-10, IL-12 and interferon-gamma (IFN-gamma) were assayed by ELISA. In both groups T cell numbers were higher in the AH than PB, although the distribution of T cell subsets in PB was similar. In the AH, CD8+ T cell numbers were higher in FHC than in IAU (P = 0.003), whilst CD4+ numbers were higher in IAU than FHC (P = 0.01). AH cytokine profiles were different in the two groups: IFN-gamma levels were higher and IL-12 levels lower in the FHC group than IAU (P = 0.02), whilst IL-10 levels tended to be higher in the FHC group (P = 0.5). We suggest that different local mechanisms governing the balance of T cell/cytokine-mediated inflammation in the anterior segment may underlie clinical differences such as chronicity and response to steroids in these disorders.
Intermediate uveitis (IU) and Fuchs' heterochromic cyclitis (FHC) are two chronic ocular inflammatory disorders. They differ considerably in ocular morbidity, which is higher in IU. T cell lines were derived from the vitreous humour (VH) and peripheral blood (PB) of 10 patients with IU and four patients with FHC. There was a predominance of CD8+ in all the lines. However, there was a significantly higher percentage of CD4+ T cells in the T cell lines derived from VH of IU (32.0 +/- 8.6%) compared with FHC patients (19. 2 +/- 8.9%) (P = 0.04). The VH-derived T cell lines (VDTC) produced significantly higher levels of IL-2, interferon-gamma (IFN-gamma) and IL-10, but not IL-4, compared with PB-derived T cell lines (PBDTC) in both entities. There was significantly higher IL-2 production by VDTC from IU when compared with FHC patients (1810 +/- 220 pg/ml versus 518 +/- 94 pg/ml; P = 0.009), which could account for the more aggressive clinical features of this condition. In contrast IL-10 production was significantly higher by the VDTC from FHC compared with IU patients. The high IL-10 production by T cells infiltrating VH of FHC patients could down-regulate the inflammatory responses, thereby contributing to the benign clinical course seen in these patients. The accumulation of T cells with differing cytokine profiles in the VH suggests an important role for these cytokines in the pathogenesis of these chronic uveitides.
The systemic secretion of rat mucosal mast cell protease (RMCPII), a major product of rat mucosal mast cells (MMC), was examined during primary infections with the protozoan parasite, Eimeria nieschulzi in CFH/B, athymic (rnu/rnu) and euthymic (rnu/+) rats. Release of RMCPII into the blood stream (2.9 micrograms/ml of serum) of normal rats occurred within 1 day after infection. This response developed 3-6 hours after inoculation with oocysts, was dose-dependent, and was found in both naive and immune rats. Maximal release of RMCPII (4.5 micrograms/ml of serum) in naive rats occurs 9 days after primary infection, whereas the numbers of MMC and concentrations of mucosal RMCPII were maximal 14 days after infection, by which time the systemic RMCPII response had begun to decline. The numbers of MMC and concentrations of mucosal RMCPII in uninfected nude rats were similar to those in the heterozygous (rnu/+) litter-mates. After infection, the numbers of MMC and concentrations of mucosal RMCPII increased in the heterozygotes but not in nude rats. Similarly, RMCPII was detected systemically only in the heterozygotes.
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