Anti-inflammation and antifibroblastic actions of interleukin-1 blockers.
Interleukin-1 (IL-1) blockers, CK 127 and CK 129, were found to inhibit IL-1-induced posterior uveitis very effectively at 3-10 mg/kg i.p. and were more potent than prednisolone which required at least 20 mg/kg i.p. to achieve the same level of anti-uveitis action. CK 127 and CK 129 were also found to be effective in inhibiting fibroblast-like corneal cells at 30-300 micrograms/ml and conjunctival cells at 0.3-10 micrograms/ml. These results indicate that IL-1 blockers are more potent in inhibiting the cell growth of conjunctival cells than that of corneal cells. From in vitro cell culture experiments, it was found that inhibition of cell growth could be due primarily to the inhibition of DNA. Although the inhibition of cell growth was due mainly to the inhibition of DNA synthesis, mRNA synthesis was also markedly inhibited. In both cells, the protein synthesis was unaffected in a few cases and markedly stimulated in most cases.
Institute of Ocular Pharmacology, Texas A&M University College of Medicine, College Station, Texas, USA.
G C
GC
Chiou
B
B
Xuan
T
T
Yamasaki
T
T
Okawara
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology; D003315:Cornea / Q000166:cytology; D004261:DNA Replication / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects*; D006834:Hydrazines / Q000494:pharmacology*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D011239:Prednisolone / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015866:Uveitis, Posterior / Q000139:chemically induced / Q000517:prevention & control*
C114708:4-benzylidenehydrazino-6-methyl-2-pyrone; C114707:5-benzylidenehydrazinopyridazin-3(2H)-one; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006834:Hydrazines; D007375:Interleukin-1; D011724:Pyridazines; D011239:Prednisolone