No abstract

Cytokines play an important role in the pathogenesis of various corneal diseases and during corneal graft rejection. Furthermore, cytokines may also play a role in the maintenance of the integrity of the normal cornea. This review focuses on the effects of several cytokines in corneal immunopathology, including the type of the corneal immune response, angiogenesis, chemotaxis, apoptosis, wound healing, corneal disease, and transplantation. It may provide clues for the future treatment of corneal disease and corneal transplantation rejection.

In view of the known anti-inflammatory activities of interleukin (IL) 10, we investigated whether the administration of recombinant murine IL-10 prolonged corneal graft survival. A major histocompatibility complex mismatched rat model with AO rats as recipients of PVG donor corneas was used. A total of 39 corneal allografts was included in this study and divided into 7 groups for different treatments. Group I (n = 6), II (n = 8), III (n = 6) and IV (n = 7) were injected subconjunctivally with saline (control), 0.5 ng, 5 ng or 50 ng of IL-10, respectively, on the day of transplantation and then on postoperative days (POD) 2, 4, 6, 8 and 10. Group V (n = 4) and group VI (n = 4) were injected intraperitoneally with saline (control) or 1 µg of IL-10, respectively, on the day before surgery, the day of grafting and then on POD 2, 4 and 6. Finally, group VII (n = 4) was injected with both subconjuctival 5 ng of IL-10 and intraperitoneal 1 µg of IL-10 on the same days as the previous groups. The median days for corneal rejection in the various groups were: group I, 11.3 ± 0.9; group II, 11.5 ± 0.9; group III, 11.6 ± 0.8, and group IV, 10 ± 1.0. Statistical analysis revealed a trend towards rejection (p = 0.08) in group IV (compared to group I). In groups V and VI, corneal rejection was evident on day 12 and in group VII the median time for rejection was 10.5 ± 0.8 days. These results indicate that IL-10 treatment does not prolong corneal allograft survival and may even accelerate rejection.

The human cornea has been shown to express a number of inflammatory cytokines including IL-1, IL-6 and IL-8. In view of the potent proinflammatory activities of interleukin-1 (IL-1), regulatory mechanisms should be present in the human cornea to control IL-1 mediated inflammatory and immune responses. This is important for the maintenance of the integrity and transparency of the cornea. To test this hypothesis, the authors determined the presence of IL-1 receptor antagonist (IL-tra) in the normal human cornea using an enzyme-linked immunosorbent assay (ELISA). IL-tra is a natural antagonist of IL-1 and competes with IL-1 for the binding to its receptors thereby blocking the inflammatory response. Corneas were either tested immediately or after a 24-hour culture period. Furthermore, the authors separately analyzed the three layers of the cornea. Their results present evidence for the constitutive expression of the IL-tra protein in the normal human cornea and show that both epithelial and stromal cells produce IL-1ra. The epithelial cells are the major source of corneal IL-1ra immunoreactivity, and secrete IL-1ra during culture. Stromal cells contain detectable, albeit low amounts of cell associated IL-1ra. No IL-1ra was detected in the endothelial cell layer. A more accurate understanding of the balance between IL-1 and IL-1ra in ocular tissues and the role of the IL-1ra under physiologie and pathophysiologic conditions will be necessary for an eventual use of IL-1 receptor antagonist as a therapeutical tool.