Effective Treatment of Experimental Uveitis with Interleukin-1 Blockers, CK 123 and CK 124

Abstract

Interleukin-1 (IL-1) blockers are known to inhibit IL-1-induced uveitis. CK 123 and CK 124 are new IL-1 blockers which showed potent anti-uveitis actions that are more potent than the classic corticosteroid, prednisolone. In addition to anti-inflammation, CK 123 and CK 124 were also found to inhibit proliferation of fibroblast-like corneal and conjunctival cells, indicating that these compounds could be used not only as anti-uveitis agents but also as useful agents to prolong the functional period of aqueous humor outflow after trabeculectomy. It was also found that DNA and mRNA synthesis were markedly inhibited by CK 123 and CK 124, yet the protein synthesis was either untouched or enhanced.

Effect of Interleukin-1 Blockers, CK112, and CK116 on Rat Experimental Choroidal Neovascularization In Vivo and Endothelial Cell Cultures In Vitro

“…Our previous work showed that CK compounds can prevent ocular inflammation, [12][13][14][15] inhibit wound healing 16 in vivo, and inhibit corneal fibroblast proliferation in vitro 15,17 through antagonizing interleukin-1 activity. 18 It is exciting to find out that this kind of compound can also inhibit the growth of CNV in the rat model and vascular endothelial cell proliferation in vitro.…”

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

“…42 Conversely, IL-1β blockers have been shown to inhibit experimental uveitis. 43 IL-6 is a macrophage-derived cytokine, also thought to be produced by endothelial and ocular parenchymal cells. 44 It is a pleiotropic cytokine that is able to function in a pro-and anti-inflammatory manner.…”

“…Readily induced by TNF-α, IFN-γ and IL-1, IL-6 has been shown to stimulate production of acute phase proteins, such as fibrinogen and C-reactive protein. 43 Evidence exists to suggest that IL-6 is involved in the direct induction of IL-2 receptor expression, differentiation and proliferation of T cells. 45 It is even thought to be more active in this respect than both IL-1 and TNF-α.…”

Anti-uveitis and inhibition of fibroblast-like corneal and conjunctival cells by interleukin-1 blockers

“…The recent discovery of synthetic IL-1 blockers which produce potent anti-inflammatory actions with few sideeffects, if any, is most exciting and warrants further studies [1,[4][5][6]. It has been found in this study that CK130 is the most potent anti-inflammatory agent of approximately 150 compounds investigated [1,[4][5][6][7][8][9][10][11].…”

“…Because of their anti-inflammatory actions, IL-1 blockers can also be used as inhibitors of fibroblast-like corneal and conjunctival cell proliferation [7][8][9][10][11][12]. If effective, these compounds could also be used to improve the success rate and functional period of cannula created after filtration surgery (trabeculectomy) in closeangle and low-tension glaucoma treatments [13,14].…”