Chemokines in acute anterior uveitis

Manju J. Verma Inflammation Research Unit, University of NSW 2052, Sydney, Australia and Cytokine Testing Laboratory, SAIC, NCI, FCRDC, Frederick, MD and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

Andrew Lloyd Inflammation Research Unit, University of NSW 2052, Sydney, Australia and Cytokine Testing Laboratory, SAIC, NCI, FCRDC, Frederick, MD and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

Helen Rager Inflammation Research Unit, University of NSW 2052, Sydney, Australia and Cytokine Testing Laboratory, SAIC, NCI, FCRDC, Frederick, MD and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

R. Robert Strieter Inflammation Research Unit, University of NSW 2052, Sydney, Australia and Cytokine Testing Laboratory, SAIC, NCI, FCRDC, Frederick, MD and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

Steven Kunkel Inflammation Research Unit, University of NSW 2052, Sydney, Australia and Cytokine Testing Laboratory, SAIC, NCI, FCRDC, Frederick, MD and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

Dennis Taub Inflammation Research Unit, University of NSW 2052, Sydney, Australia and Cytokine Testing Laboratory, SAIC, NCI, FCRDC, Frederick, MD and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

Denis Wakefield Inflammation Research Unit, University of NSW 2052, Sydney, Australia and Cytokine Testing Laboratory, SAIC, NCI, FCRDC, Frederick, MD and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

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Abstract

PURPOSE. The aim of this study was to define the expression of chemoattractant cytokines (chemokines) in human aqueous humor, obtained from patients with idiopathic acute anterior uveitis (AU). The chemokines assayed included macrophage inflammatory proteins-1a and -1ß (MIP-1a and -1ß), monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interferon-inducible protein-10 (IP-10), and regulated on activation, normal T-expressed and secreted (RANTES). METHODS. We studied fifteen patients (7 females) with idiopathic acute AU, at various stages of disease activity, and two control subjects undergoing elective cataract extraction. Aqueous humor was collected under aseptic conditions, after obtaining informed consent. Chemokine concentrations were measured using specific ELISA. Correlation was sought between chemokine concentrations and disease activity, evaluated by slit lamp biomicroscopy and graded using a standardized scale of disease severity. RESULTS. IL-8 was detected (35.9 ± 13.6, mean ± SE) in three of seven subjectes in active, untreated stages of AU (clinical score 2–4), and it was undetectable in subjects sampled in the quiescent phase of the disease. IP-10 had a mean concentration of 40.6 ng/ml ± 20.9 in the active group (N = 7), declining to 0.8 ng/ml ± 0.3 in the samples from patients with inactive disease (N = 7, P = 0.001). Similarly, substantial expression of MCP-1 was noted, with a maximum concentration of 145 ng/ml, in acute (active) AU (N = 6), (26.7 ± 19.7), falling to undetectable levels in those with inactive disease, and in control subjects (P = 0.001). MIP-1ß (N = 7), (3.4 ± 1.5, P = 0.001) and RANTES (N = 7, 8.8 ± 4.2) levels were significantly increased in acute disease (P = 0.001) and related to the activity of the disease, although the concentrations were not as high as MCP-1, IP-10 and IL-8. IP-10, RANTES and MIP-1ß were detected at low concentrations in the aqueous humor of the control subjects. CONCLUSIONS. This is the first study of chemokine concentrations in the aqueous humor of patients with acute anterior uveitis. The concentration of chemokines: IL-8, IP-10, MCP-1, RANTES and MIP-1ß were significantly increased during the active stages of AU, and correlated with the clinical severity of the disease. These chemoattractant cytokines probably play a critical role in leucocyte recruitment in acute AU.

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Chemokines in acute anterior uveitis

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Chemokines in acute anterior uveitis

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