Chemokines in the limbal form of vernal keratoconjunctivitis

Background/aims-Chemokines are a family of low molecular weight cytokines t hat attract and activate leucocytes. The CC chemokines act on eosinophils, basophils, monocytes, and lymphocytes, suggesting that they play an importa nt part in allergic diseases. The aims of this study were to investigate th e expression of the CC chemokines, RANTES, eotaxin, monocyte chemotactic pr otein (MCP) 1, MCP-2, and MCP-S in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and to determine the cellular source of these ch emokines. Methods-Conjunctival biopsy specimens from nine subjects with active VKC, a nd six control subjects were studied by immunohistochemical techniques usin g a panel of monoclonal and polyclonal antibodies directed against RANTES, eotaxin, MCP-1, MCP-2, and MCP-3. The phenotype of inflammatory cells expre ssing chemokines was examined by sequential double immunohistochemistry. Results-In the normal conjunctiva, superficial epithelial cells showed a co nstitutive, weak cytoplasmic expression of eotaxin. Few inflammatory cells in the perivascular areas expressed RANTES, MCP-1, MCP-2, and MCP-3. In VKC specimens, the epithelium showed intense cytoplasmic eotaxin staining in a ll cells, and cytoplasmic RANTES staining mainly in the superficial layers. Furthermore, RANTES and eotaxin were expressed on the vascular endothelium mainly in the upper substantia propria. Compared with normal controls, VKC specimens showed significantly more inflammatory cells expressing RANTES, eotaxin, MCP-1, and MCP-3 (p<0.001, 0.0028, 0.0092, and <0.001, respectivel y). In VKC specimens, the numbers of inflammatory cells expressing RANTES w ere significantly higher than the numbers of inflammatory cells expressing eotaxin, MCP-1, and MCP-2 (all p values <0.001). Colocalisation studies rev ealed that the majority of inflammatory cells expressing chemokines were CD 68 positive monocytes/macrophages. Conclusions-These results demonstrate an increase in the expression of RANT ES, eotaxin, MCP-1, and MCP-3 in the conjunctiva of patients with VKC compa red with control subjects. These data suggest a potential role for these ch emokines in the pathogenesis of VKC. Antagonists of chemokine receptors may provide new therapeutic modalities in VKC.