Anti-inflammatory and immunomodulatory effects of RDV-8 [C18H22N2O2S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] in a rat model of induced pleurisy and in vitro lymphoproliferation

Inflammopharmacology. 2011 Jun;19(3):145-53. doi: 10.1007/s10787-010-0063-3. Epub 2010 Oct 28.

Abstract

RDV-8 [C(18)H(22)N(2)O(2)S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] is derived from the 4-thioxopyrimidine, and presents important clinical effects. The present study explored the RDV-8 effects in the proliferation of human peripheral blood mononuclear cells (PBMCs), as well as in a pleurisy-induced rat model. PBMCs were directly plated in four different RDV-8 concentrations (0.0125, 0.025, 0.05 and 0.1 mg/mL). RDV-8 decreased cell proliferation and monocyte chemotactic protein 1 synthesis. The interleukin 1 levels and the cytotoxic effect were not significantly affected by RDV-8 treatment. In the carrageenan-induced pleurisy model, the RDV-8 (3 mg/kg) treatment induced a significant reduction in the exudate volume, in the polymorphonuclear leukocyte migration and in the pleural exudate NO levels. The results indicate that RDV-8 may have an immunomodulatory effect, as well as anti-inflammatory actions suggesting that it could represent a new strategy in the inflammatory response modulation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Carrageenan
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / pharmacology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Nitric Oxide / metabolism
  • Pleurisy / drug therapy*
  • Pleurisy / physiopathology
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Thiones / administration & dosage
  • Thiones / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Chemokine CCL2
  • Immunologic Factors
  • Pyrimidines
  • Thiones
  • ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate
  • Nitric Oxide
  • Carrageenan