Conjunctival fibrosis in ocular cicatricial pemphigoid--the role of cytokines.

Ocular cicatricial pemphigoid (OCP) is a systemic, autoimmune disease characterised by conjunctival scarring that is often progressive. The pathophysiology of the fibrosis is unknown. This study aimed to determine which fibrogenic cytokines are present in the conjunctiva in patients with acute and chronic OCP as a first stage in determining the mechanisms of fibrosis. Conjunctival biopsies from patients with acute, subacute and chronic OCP (n=13) were compared to normal conjunctiva (n=10). Production of mRNA for, and expression of, transforming growth-beta1, 2 and 3 (TGF-beta), TGF-beta receptor, platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) were assessed using in situ hybridisation and immunohistochemistry. Acute disease showed increased levels of mRNA for TGF-beta1 and 3, mainly in stromal fibroblasts and macrophages. In the stroma, there were concordant increases in latent and activated TGF-beta1 and 3 and TGF-beta receptor expression by fibroblasts. There were no significant increases in the expression of TGF-beta2, PDGF or FGF in acute disease. No cytokines or receptors were significantly increased in chronic disease. Acutely inflamed conjunctiva in OCP is associated with significant stromal levels of TGF-beta1 and 3 but not PDGF or FGF and none were increased in chronic disease. This suggests that TGF-beta may have a key role in the pathogenesis of the fibrosis. The absence of fibrogenic cytokines in chronic progressive OCP provides support for the proposal that fibroblasts in OCP conjunctiva may remain functionally and morphologically abnormal after the withdrawal of cytokine influences.