Effects of interleukin-1 blockers on corneal fibroblast proliferation in vitro and ocular inflammation in vivo

The success of keratorefractive surgical procedures is limited by the wound healing process in the corneal stroma. The proliferation and matrix synthe sis of corneal stromal fibroblasts is the central element of the wound heal ing process that is triggered by an initial inflammation. In order to devel op new therapeutic strategies to reduce wound healing intensity, we investi gated the effect of newly synthesized interleukin-1 (IL-1) blockers on the proliferation of cultured rabbit corneal fibroblasts and the ocular inflamm ation induced by IL-1. It was found that the addition of IL-1 blockers, suc h as CK-135 to CK-145, led to a dose-dependent inhibition of cell prolifera tion after 24, 48 and 72 hr of incubation. The isotope incorporation study showed that the syntheses of DNA and mRNA were suppressed whereas that of p rotein was enhanced or unaffected. These compounds also demonstrated a pote nt anti-inflammation action in the rat uveitis model. Our results indicate that CK (Chiou-Kumamoto) compounds may be valuable therapeutic agents for t he prevention of postoperative complications after corneal keratorefractive surgical procedures.