Tumour necrosis factor alpha and interleukin 6 gene expression in keratocytes from patients with rheumatoid corneal ulcerations.

BACKGROUND/AIMS: Ultrastructural alterations in the stroma adjacent to corneal perforations have previously been reported in patients with longstanding rheumatoid arthritis. Since patients with rheumatoid arthritis often present upregulation of proinflammatory cytokines in serum and in synovial fluid, it was of interest to analyse the gene expression of these cytokines-for example, tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), in corneal samples from patients with corneal ulcerations and/or perforations associated with rheumatoid arthritis. METHODS: Corneal samples from seven patients with corneal ulcerations and/or perforations associated with rheumatoid arthritis were collected in 4% paraformaldehyde in "RNAse-free" conditions. Paraffin sections were fixed on silan coated slides and further analysed by systematic non-radioactive in situ hybridisation, using specific gene probes for TNF-alpha and IL-6 labelled with digoxigenin (DIG). Detection of hybrids was carried out by using a commercially available DIG detection system. RESULTS: Whereas an extended TNF-alpha gene expression could be clearly observed in the keratocytes surrounding the corneal ulcerations and/or perforations from five of the seven analysed patients, all seven patients presented clearly positive results for an extended IL-6 gene expression in the analysed tissue samples. CONCLUSIONS: Alterations in corneal cells surrounding ulcerations and/or perforations in patients with rheumatoid arthritis may occur with implication for inflammatory processes. Upregulation of the proinflammatory cytokines TNF-alpha and IL-6 may modify the production of metalloproteinases in the corresponding cells resulting in collagenolytic corneal damage.