Effects of leflunomide on the course of listeriosis in mice. Short communication.
The intensity of an infection with Listeria monocytogenes depends on the immunological stab1p4f the body. Impairment of the specific or unspecific defence can lead to severe and partly fatal complications such as meningitis or septicaemia. In a normal defence situation affected individuals are often not diagnosed because the infection appears as an unspecific indisposition. The new immunomodulator leflunomide (n-(4-trifluoro-methyl-phenyl)-5-methyl-isoxazol-4-carboxamide, CAS 75706-12-6, HWA 486) acts mainly as immunosuppressive. Therefore, the influence of leflunomide was investigated on the number of spleen bacteria in the first phase and on the lethality in both phases of mouse listeriosis. The infected mice were either in a normal defence state or in an immunocompromised situation, which was produced by injection of cyclophosphamide or by dextran sulfate. A treatment with leflunomide, 20 mg/kg i.p., twice daily over a period of 3 days, caused no change of the lethality compared with control mice. Likewise, combined administration of leflunomide and ampicillin produced no alteration of the lethal outcomes in comparison with the ampicillin medication alone, the latter being highly effective in any case. However, the number of spleen bacteria was significantly higher in the group with combined treatment than in the ampicillin group. In summary, the treatment with leflunomide most likely will cause no additional risk regarding an infection such as listeriosis, although in the case of an infection an increased care should be given to diagnostic and therapy.
Hirschelmann
R
R
Institut Pharmakologie für Naturwissenschaftler, Martin-Luther-Universität Halle-Wittenberg, Germany.
Staffeldt
D
D
Wilhelms
D
D
Sandow
D
D
Schleyerbach
R
R
D000667:Ampicillin / Q000627:therapeutic use; D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D016264:Dextran Sulfate / Q000494:pharmacology; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D008088:Listeriosis / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D013154:Spleen / Q000382:microbiology
D007166:Immunosuppressive Agents; D007555:Isoxazoles; D000667:Ampicillin; D003520:Cyclophosphamide; D016264:Dextran Sulfate; D000077339:Leflunomide