Antagonism of interleukin-1 (IL-1)-induced uveitis with synthetic IL-1 blockers

J Ocul Pharmacol Ther. 1997 Oct;13(5):427-33. doi: 10.1089/jop.1997.13.427.

Abstract

Because of the discovery of potent interleukin-1 (IL-1) blocking effects by CK-103A (4,6-dihydropyridazino[4,5-c]pyridazin-5 (1H)-ones) on rat uveitis induced by IL-1, numerous derivatives of CK-103A have been synthesized and their efficacies on the same animal model studied. The uveitis was induced by injection of 1 ng IL-1/10 microliters intravitreally. The inflammation reached peak at 12 hr after the injection of IL-1. The prevention/blockade of IL-1-induced uveitis was measured at this peak inflammation time point. It was found that 8 out of 12 CK-analogs studied produced an effective blockade of IL-1-induced uveitis. Most of them were at least equipotent or even more potent than prednisolone in blocking IL-1-induced uveitis. It is concluded that most dihydropyridazinopyridazin derivatives are effective anti-uveitis compounds. Some could be found to be safe and useful for the treatment of this dreadful disease.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Female
  • Interleukin-1 / antagonists & inhibitors*
  • Pyridazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Uveitis / chemically induced*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • CK 103A
  • Interleukin-1
  • Pyridazines