Suppression of Interleukin-1α-Induced Uveitis and Inhibition of Fibroblast-like Cell Proliferation by Synthetic Interleukin-1 Blockers

Abstract

To treat uveitis and prolong the functional life of filtration surgery on glaucomatous eyes, some interleukin-1 (IL-1) blockers were used to inhibit IL-1-induced uveitis in rat eyes and to suppress proliferation of fibroblast-like corneal and conjunctival cells in the cell cultures, respectively. It was found in this research that the blood-aqueous barrier can be broken by IL-1alpha to allow fluorescein to enter the eyeballs and to be detected by fluorotron. The uveitis was effectively blocked by the IL-1 blockers studied in this research. It was also noted that the proliferation of fibroblast-like corneal and conjunctival cells was effectively inhibited by IL-1 blockers. The inhibition of cell growth seems to be caused primarily by the inhibition of RNA synthesis. There was a significant difference in the potency of IL-1 blockers to inhibit corneal vs. conjunctival cells. It was noted that conjunctival cells were more easily inhibited by IL-1 blockers than corneal cells. These results indicate that IL-1 blockers can suppress the proliferation of conjunctival cells at dose levels which do not affect the normal cell growth of corneal cells.

The effect of IL-l.ALPHA. and nifedipine of cell proliferation and DNA synthesis in cultured human gingival fibroblasts

“…Several studies have also shown that IL-1 is a potent stimulator of fibroblast proliferation (5,(7)(8)(9)26,27), and Inokuchi et al (28) demonstrated that IL-1α stimulates cell proliferation through Ca 2+ /calmodulindependent pathway in NIM 1 cells, a human thyroid cell line established from a patient with thyroid papillary adenocarcinoma. The findings of recent papers that the IL-1 blockers, CK-119 and CK-122 (29) and 1-methyl hydrazine analogs (30,31) inhibit the cell proliferation in human lung fibroblasts and fibroblast-like cells, respectively, also suggest that IL-1 enhances cell growth in fibroblasts.…”

Peribulbar poloxamer for ocular drug delivery

“…Fluorotron provides a non‐invasive technique for measuring the fluorescence content along the axes of eye during the time period under study and has been used to evaluate the blood–aqueous barrier (Wu et al. 1995; Chiou et al. 1999; Carmo et al.…”

Inhibition of Interleukin-1-Induced Uveitis and Corneal Fibroblast Proliferation by Interleukin-1 Blockers

“…To date, numerous synthetic compounds have been found to produce effective inhibitory actions on interleukin-1 (IL-1 )-induced uveitis and corneal fibroblast proliferation (1)(2)(3)(4)(5)(6)(7)(8). Among them, 1-methyl hydrazino derivatives were found to be most potent and promising (4)(5)(6)(7)(8).…”

“…Among them, 1-methyl hydrazino derivatives were found to be most potent and promising (4)(5)(6)(7)(8). They could be used for the treatment/prevention of IL-1 -induced uveitis, scar formation after glaucoma filtration surgery (9,10) and myopia's photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) (8,11,12).…”