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Institute of Virology, Erasmus Medical Center, Rotterdam, The Netherlands
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-
, and IFN-
-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- 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-- and IFN--induced secretion of
macrophage-inflammatory proteins 1 and 3, while inhibiting the
induced secretion of RANTES. Furthermore, considerable levels of
IFN--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.
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