Molecular analysis of resolving immune responses in uveitis

To identify the cellular immune processes underlying intra-ocular inflammat ion, 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-1 beta, IL-2, IL-4, IL-6, IL-10, IL-12, in terferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta); T c ell subsets CD3, CD4, CD8; monocytes and macrophages (CD14); and B cells (C D19) was measured using reverse transcriptase-polymerase chain reaction (RT -PCR) and radiometric analysis. The majority of uveitis patients demonstrat ed 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 num ber of patients with age-related cataract. This Th1-like polarization was s upported by an increased expression of CD8 in a number of patients. IL-1 be ta was expressed in only six uveitic eyes. Only four patients expressed eit her IL-4 or IL-10 and no patient expressed both. TGF-beta mRNA could be det ected 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 s ample. The cellular infiltrate in the uveitic eyes showed clear evidence of low IL-1 and absent IL-12 expression despite a Th1-like profile sand high expression of macrophages. This strongly suggests that the systemic immunos uppressive therapy used prior to surgery in some patients and/or the chroni city of the uveitis had actively suppressed/switched off macrophage functio n, leading to resolution of T cell activity.