Antiuveitis and inhibition of fibroblast-like corneal and conjunctival cell cultures by interleukin-1 blockers, CK 125, CK 126 and CK 128.
Three new interleukin-1 (IL-1) blockers, CK 125, CK 126 and CK 128, were studied for their effects on IL-1-induced uveitis in rat eyes. They were more potent (at 3-10 mg/kg t.i.d.) than prednisolone (20 mg/kg t.i.d.) in effectively inhibiting posterior uveitis. They were also found to inhibit fibroblast-like corneal cells at 10-300 micrograms/ml concentrations and conjunctival cells at 1-30 micrograms/ml levels. The incorporation of leucine into corneal and conjunctival cells was either stimulated or unaffected by CK 126, indicating that the inhibition of cell growth has nothing to do with the protein synthesis. However, the incorporation of uridine into corneal and conjunctival cells was markedly inhibited by CK 126 at 3-30 micrograms/ml concentrations whereas the incorporation of thymidine into the cells was inhibited at a lesser extent than that of uridine. These results indicate that cell inhibition by CK 126 could be related mainly to the synthesis of mRNA and, to a lesser extent, to DNA synthesis.
Xuan
B
B
Institute of Ocular Pharmacology, Texas A&M University College of Medicine, College Station 77843-1114, USA.
Chiou
G C
GC
Yamasaki
T
T
Okawara
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003315:Cornea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D007375:Interleukin-1; D007930:Leucine / Q000378:metabolism; D011239:Prednisolone; D011724:Pyridazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D013936:Thymidine / Q000378:metabolism; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology; D014529:Uridine / Q000378:metabolism; D015866:Uveitis, Posterior / Q000139:chemically induced / Q000517:prevention & control*
C113251:2-benzyl-5-benzylidene-hydrazinopyridazin-3(2H)-one; C113205:5-benzylidenehydrazino-2-phenylpyridazin-3(2H)-one; C113252:6-benzylidenehydrazino-1,3-dimethyluracil; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006834:Hydrazines; D007375:Interleukin-1; D011724:Pyridazines; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D014498:Uracil; D004247:DNA; D011239:Prednisolone; D007930:Leucine; D013936:Thymidine; D014529:Uridine