Differential effects of phosphodiesterase type 4-specific inhibition on human autoreactive myelin-specific T cell clones.
Proinflammatory cytokines, secreted by autoreactive CD4+ T lymphocytes may contribute to the pathogenesis of several human autoimmune diseases, including multiple sclerosis (MS). Since the antigen specificities of these T cells are not known at present, therapeutic strategies aiming at common effector pathways, in particular cytokine secretion, may be more feasible in the near future. We have studied the influence of the isoenzyme-specific phosphodiesterase inhibitor rolipram on the proliferation and cytokine secretion of human myelin basic protein-specific T cell clones. The inhibition of proliferation correlated with interference with the IL-2/IL-2 receptor system, while the effects of rolipram on several T helper 1-(TNF-alpha, TNF-beta, IFN-gamma) and T helper 2-like cytokines (IL-4, IL-13) as well as IL-10 revealed an interesting drug profile, with preferential inhibition of TNF-beta, TNF-alpha and IL-10. This profile suggest that rolipram differs from other currently used immunomodulatory drugs.
Pette
M
M
Neuroimmunology Branch, National Institute for Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. mpette@fnz.med.tu-dresden.de
Muraro
P A
PA
Pette
D F
DF
Dinter
H
H
McFarland
H F
HF
Martin
R
R
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000235:genetics; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000906:Antibodies; D001324:Autoantigens / Q000276:immunology*; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002999:Clone Cells; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology; D009185:Myelin Proteins / Q000276:immunology*; D009186:Myelin Sheath / Q000737:chemistry / Q000276:immunology; D015345:Oligonucleotide Probes; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000276:immunology; D020889:Rolipram; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000906:Antibodies; D001324:Autoantigens; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D009185:Myelin Proteins; D015345:Oligonucleotide Probes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram