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 synthesis of corneal stromal fibroblasts is the central element of the wound healing process that is triggered by an initial inflammation. In order to develop new therapeutic strategies to reduce wound healing intensity, we investigated the effect of newly synthesized interleukin-1 (IL-1) blockers on the proliferation of cultured rabbit corneal fibroblasts and the ocular inflammation induced by IL-1. It was found that the addition of IL-1 blockers, such as CK-135 to CK-145, led to a dose-dependent inhibition of cell proliferation after 24, 48 and 72 hr of incubation. The isotope incorporation study showed that the syntheses ofDNA and mRNA were suppressed whereas that of protein was enhanced or unaffected. These compounds also demonstrated a potent anti-inflammation action in the rat uveitis model. Our results indicate that CK (Chiou-Kumamoto) compounds may be valuable therapeutic agents for the prevention of postoperative complications after corneal keratorefractive surgical procedures.

[1]  G. Chiou,et al.  Suppression of interleukin-1alpha-induced uveitis and inhibition of fibroblast-like cell proliferation by synthetic interleukin-1 blockers. , 1999, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[2]  W. Petroll,et al.  Corneal stromal wound healing in refractive surgery: the role of myofibroblasts , 1999, Progress in Retinal and Eye Research.

[3]  T. Okawara,et al.  A new approach to fused 1,2-diazepines by cyclization of enhydrazines with α- and β-keto esters , 1998 .

[4]  G. Chiou,et al.  Antagonism of interleukin-1 (IL-1)-induced uveitis with synthetic IL-1 blockers. , 1997, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[5]  R. Bahn,et al.  Interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptor inhibit IL-1-induced glycosaminoglycan production in cultured human orbital fibroblasts from patients with Graves' ophthalmopathy. , 1996, The Journal of clinical endocrinology and metabolism.

[6]  P. McDonnell,et al.  Effect of diclofenac on corneal haze after photorefractive keratectomy in rabbits. , 1995, Ophthalmology.

[7]  G. Chiou,et al.  Novel non-arachidonate-mediated, non-steroidal anti-inflammatory agents , 1994 .

[8]  J. Rosenbaum,et al.  Activity of an interleukin 1 receptor antagonist in rabbit models of uveitis. , 1992, Archives of ophthalmology.

[9]  Y. Pouliquen,et al.  Binding sites for human interleukin 1 alpha, gamma interferon and tumor necrosis factor on cultured fibroblasts of normal cornea and keratoconus. , 1991, Current eye research.

[10]  W M Petroll,et al.  Neutralizing antibody to TGFbeta modulates stromal fibrosis but not regression of photoablative effect following PRK. , 1998, Current eye research.

[11]  G. Chiou,et al.  Effects of interleukin-1 blockers on ophthalmic wound healing in a rabbit model of trabeculectomy. , 1995, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[12]  D. Gartry,et al.  The effect of topical corticosteroids on refraction and corneal haze following excimer laser treatment of myopia: An update. A prospective, randomised, double-masked study , 1993, Eye.