Effects of rolipram on release of inflammatory cytokines in vitro by peritoneal macrophages extracted from adjuvant arthritis rats

Objective To explore the effects of selective phosphodiesterase(PDE) 4 inhibitor rolipram on lipopolysaccharide(LPS)-induced releasing of proinflammatory cytokines tumor necrosis factor alpha(TNF-α),interleukin 1 beta(IL-1β) in vitro by peritoneal macrophages(PM) extracted from adjuvant arthritis(AA) rats.Methods AA rat model and normal control were prepared,then PM were collected and cultured in vitro,LPS was administrated and different concentrations of rolipram were added at the same time.Levels of TNF-α,IL-1β in cell culture supernatant were assayed by enzyme-linked immunosorbent assay(ELISA),and intracellular expression of TNF-α mRNA,IL-1β mRNA were determined by reverse transcription-polymerase chain reaction(RT-PCR).Results TNF-α,IL-1β in PM culture supernatants,intracellular expression of TNF-α mRNA,IL-1β mRNA of AA rats were significantly higher than those of normal rats,(386.80±63.24) ng/L vs(48.53±6.47) ng/L(P0.01),(317.77±29.33) ng/L vs(77.75±11.60) ng/L(P0.01),77.92±12.55 vs 15.97±4.37(P0.01),49.30±10.06 vs 10.15±1.34(P0.01) respectively.Rolipram in a dose-dependent manner inhibited the LPS-stimulated expression of TNF-α mRNA,IL-1β mRNA,and inhibited TNF-α,IL-1β production in AA rats.Conclusion Rolipram can inhibit LPS-induced releasing of pro-inflammatory cytokines ex vitro by PM extracted from AA rats,suggested that the selective PDE4 inhibitors may be used in the treatment of RA by inhibiting the inflammatory reaction.