The effect of rolipram on the production of cytokines in HTLV-I infected cell lines and peripheral blood mononuclear cells of patients with HTLV-I-associated myelopathy (HAM).
Previous studies have reported that the levels of pro-inflammatory cytokines, such as TNF-alpha and IFN-gamma, are elevated in the serum as well as in the cerebrospinal fluid of HAM/TSP patients. To evaluate the effect of the phosphodiesterase type IV inhibitor, rolipram on cytokine production, peripheral blood mononuclear cells (PBMCs) of HAM/TSP patients or HTLV-I infected T-cell lines (HUT102, MT2) were cultured in the presence of different doses of rolipram. The amount of cytokines in the supernatants of the cultured cells was determined by ELISA for TNF-alpha, IFN-gamma and TGF-beta. Rolipram inhibited TNF-alpha production by HUT102 and PBMCs from all the HAM/TSP patients in a dose-dependent manner. The suppression of IFN-gamma varied and was weaker in some HAM/TSP patients compared to that of TNF-alpha. The concentration of TGF-beta in the culture supernatants was not influenced by rolipram. The levels of TNF-alpha mRNA determined by competitive PCR were not changed in the cultured cells in the presence of rolipram, suggesting that rolipram inhibits TNF-alpha production at the post-transcriptional level. These findings suggest the possible benefit of rolipram as a therapeutic agent for HAM/TSP patients.
Hatae
T
T
Department of Neurology, Faculty of Medicine, Kyushu University, Fukuoka city, Fukuoka, Japan.
Hara
H
H
Kobayashi
T
T
Watanabe
T
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D015493:Paraparesis, Tropical Spastic / Q000188:drug therapy* / Q000821:virology; D010431:Pentoxifylline / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D011760:Pyrrolidinones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D020889:Rolipram; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D020889:Rolipram; D010431:Pentoxifylline