Herpetic stromal keratitis (HSK) is an immunopathologic disease triggered by infection of the cornea with HSV. Key events in HSK involve the interaction between cornea-infiltrating inflammatory cells and resident cells. This interaction, in which macrophages, producing IL-1 and TNF-alpha, and IFN-gamma-producing Th1 cells play a crucial role, results in the local secretion of immune-modulatory factors and a major influx of neutrophils causing corneal lesions and blindness. The Th1-derived cytokine IL-17 has been shown to play an important role in several inflammatory diseases characterized by a massive infiltration of neutrophils into inflamed tissue. Here we show that IL-17 is expressed in corneas from patients with HSK and that the IL-17R is constitutively expressed by human corneal fibroblasts (HCF). IL-17 exhibited a strong synergistic effect with TNF-alpha on the induction of IL-6 and IL-8 secretion by cultured HCF. Secreted IL-8 in these cultures had a strong chemotactic effect on neutrophils. IL-17 also enhanced TNF-alpha- and IFN-gamma-induced secretion of macrophage-inflammatory proteins 1alpha and 3alpha, while inhibiting the induced secretion of RANTES. Furthermore, considerable levels of IFN-gamma-inducible protein 10 and matrix metalloproteinase 1 were measured in stimulated HCF cultures, while the constitutive secretion of monocyte chemotactic protein 1 remained unaffected. The data presented suggest that IL-17 may play an important role in the induction and/or perpetuation of the immunopathologic processes in human HSK by modulating the secretion of proinflammatory and neutrophil chemotactic factors by corneal resident fibroblasts

Adjuvants, Immunologic/*biosynthesis/metabolism/pharmacology/physiology, Cell Line, Cells, Cultured, Chemokines/*biosynthesis/secretion, Cornea/*immunology/*metabolism/pathology, Drug Synergism, Fibroblasts/enzymology/*immunology/*metabolism/secretion, Humans, Interleukin-17/*biosynthesis/metabolism/pharmacology/physiology, Interleukin-6/secretion, Interleukin-8/physiology/secretion, Interstitial Collagenase/secretion, Keratitis, Herpetic/*immunology/pathology, Neutrophil Infiltration/immunology, Receptors, Interleukin/biosynthesis, Recombinant Proteins/biosynthesis, Research Support, Non-U.S. Gov't, Stromal Cells/immunology/metabolism/pathology, T-Lymphocyte Subsets/immunology/metabolism/pathology, Tumor Necrosis Factor-alpha/pharmacology
Journal of Immunology
Erasmus MC: University Medical Center Rotterdam

Maertzdorf, J, Osterhaus, A.D.M.E, & Verjans, G.M.G.M. (2002). IL-17 expression in human herpetic stromal keratitis: modulatory effects on chemokine production by corneal fibroblasts. Journal of Immunology. Retrieved from http://hdl.handle.net/1765/10014