Molecular analysis of resolving immune responses in uveitis

To identify the cellular immune processes underlying intra-ocular inflammation, aqueous humour was obtained at cataract surgery from 22 patients with clinically inactive uveitis and 24 patients with age-related cataract. mRNA expression for the cytokines IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta); T cell subsets CD3, CD4, CD8; monocytes and macrophages (CD14); and B cells (CD19) was measured using reverse transcriptase-polymerase chain reaction (RT-PCR) and radiometric analysis. The majority of uveitis patients demonstrated a T cell-mediated inflammatory response, predominately involving a Th1-like cytokine profile with expression of IL-2 and IFN-gamma in 16/22 and 18/22 samples, respectively. These cytokines were present in only a small number of patients with age-related cataract. This Th1-like polarization was supported by an increased expression of CD8 in a number of patients. IL-1beta was expressed in only six uveitic eyes. Only four patients expressed either IL-4 or IL-10 and no patient expressed both. TGF-beta mRNA could be detected in 18/22 uveitis patients and 15/24 controls. IL-12, the paradigmatic Th1-inducing cytokine, was absent in all samples but CD14 was expressed in the majority of patients and controls. CD19 could not be detected in any sample. The cellular infiltrate in the uveitic eyes showed clear evidence of low IL-1 and absent IL-12 expression despite a Th1-like profile and high expression of macrophages. This strongly suggests that the systemic immunosuppressive therapy used prior to surgery in some patients and/or the chronicity of the uveitis had actively suppressed/switched off macrophage function, leading to resolution of T cell activity.