Selective regulation of T cell IL-5 synthesis by OM-01, JTE-711 and p38 MAP kinase inhibitor: independent control of Th2 cytokines, IL-4 and IL-5.
BACKGROUND
Helper T cells are involved in chronic eosinophilic inflammation. Control of cytokine production seems to be an effective management.


METHODS
The effect of nonactin, SB203580, a p38 MAP kinase inhibitor, and JTE-711 on the cytokine production of allergen-specific T cell clones was determined. The effect of nonactin on the airway eosinophilia was investigated using murine asthma model.


RESULTS
Nonactin suppressed IL-5 synthesis by human Th cells in a dose-dependent manner without affecting IL-2 or IL-4 synthesis, and still significantly suppressed murine airway eosinophilia induced by the antigen inhalation. SB203580 and JTE-711 also selectively inhibited IL-5 synthesis in vitro.


CONCLUSIONS
Synthesis of IL-5 by human Th cells can be differentially regulated from that of other major T cell cytokines. The in vivo effects of selective IL-5 synthesis inhibitors suggest that IL-5 is the reasonable target for the regulation of allergic disorders accompanied by eosinophilic inflammation.
Mori
A
A
Clinical Research Center, National Sagamihara Hospital, Sagamihara, Kanagawa, Japan. mori-kkr@umin.ac.jp
Okudaira
H
H
Kobayashi
N
N
Akiyama
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy; D002999:Clone Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis*; D018942:Macrolides / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D018448:Models, Immunological; D010797:Phthalimides / Q000494:pharmacology*; D011657:Pulmonary Eosinophilia / Q000188:drug therapy; D011725:Pyridines / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D015848:Interleukin-5; C425789:JTE-711; D018942:Macrolides; D010797:Phthalimides; D011725:Pyridines; D015847:Interleukin-4; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C050476:nonactin