title: Effects of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice.
abstract: The present study was designed to investigate the effect of the phosphodiesterase IV inhibitor rolipram on Th1 and Th2 immune responses in mice. Mice were immunized subcutaneously at the base of the tail with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0) and were treated daily with oral administration of various doses of rolipram from days 0 to 20. On day 21, production of anti-OVA IgG and proliferative responses to the antigen were determined. Anti-OVA IgG2a and interferon-gamma (IFN-gamma), as indicators of Th1 responses, and anti-OVA IgG1 and interleukin-10 (IL-10), as indicators of Th2 responses, were also measured. The results showed that treatment with rolipram failed to affect the production of OVA-specific IgG but decreased the proliferation of spleen cells to the antigen. Its inhibitory effect on these immune responses was correlated with a marked decrease in IFN-gamma but not IL-10 production, although neither anti-OVA IgG2a nor IgG1 production was affected by rolipram. These results suggest that rolipram may preferentially inhibit Th1 responses more effectively than Th2 responses. Administration of rolipram resulted in suppression of antigen (OVA)-induced arthritis in mice. The suppression of joint inflammation by rolipram was associated with the inhibition of the OVA-specific proliferative responses of spleen cells and IFN-gamma secretion. These results indicate that rolipram may be effective in regulating Th1-mediated diseases such as rheumatoid arthritis.
authors.affiliation: Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Hyogo 658-8558, Japan.
authors.forename: Kouya
authors.initials: K
authors.lastname: Yamaki
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Li
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.forename: A H M Khurshid
authors.initials: AH
authors.lastname: Alam
authors.forename: Md Aslam
authors.initials: MA
authors.lastname: Hossain
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Shinji
authors.initials: S
authors.lastname: Taneda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Yoki
authors.initials: Y
authors.lastname: Mori
authors.forename: Shin
authors.initials: S
authors.lastname: Yoshino
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D001168:Arthritis / Q000188:drug therapy / Q000276:immunology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D005260:Female; D005620:Freund's Adjuvant; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D016753:Interleukin-10 / Q000037:antagonists & inhibitors; D051379:Mice; D010047:Ovalbumin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D020889:Rolipram / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D010726:Phosphodiesterase Inhibitors; D016753:Interleukin-10; D007371:Interferon-gamma; D010047:Ovalbumin; D005620:Freund's Adjuvant; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram