The efficacy of umf 078 onAcanthocheilonema viteaeandLitomosoides sigmodontisinMeriones unguiculatus

Abstract

In experiment B, where the pumps were removed, the leu cocyte counts increased again.These animals, treated with interferon-y prior to infection, showed higher immunoglobulin titers (IgG and IgM) in the early phase of infection. After one week of treatment, at the day of infection, the neutrophil counts were significantly increased, whereas the eosinophils were reduced during the first 14 days. Up to week 20 p.i. microfilaridermia rea ched titers which were twice as high as in the control group, but this difference was not significant. Fotir of the treated and two of the control animals were dissected 35 weeks post infection in order to carry out lymphocyte transformation tests. No differences were seen between the treated and the untreated control group. Macrophages (McJ>) isolated from the peritoneum of patent animals showed a high baseline proliferation, whereas coincubation of M<D's with spleen cells resulted in a lower proliferation. In both cases proliferation could be increased by the addition of filarial antigen or Phytohemagglutinin (PHA). However, the presence of IFN-y reduced the prolife ration to baseline or lower levels. Despite this proliferation inhibiting effect, IFN-y enables macrophages to kill microfi lariae in vitro within one to three days. The production of nitric oxide by IFN-y activated MO's could be shown. DISCUSSION AND CONCLUSIONI mplantation of osmotic pumps is a suitable method for the application of short lived substances like IFN-y or other cytokines. Drugs can be delivered satisfactorally as well. Drugs and cytokines administered in this way had the same or an even better efficacy than injected ones (Murray, 1990, own observation). Other implantation sites in the ani mal can be used, if there is sufficient space for the pump.The pocket should be large enough and about 1 cm longer than the pump. This prevents the pump from resting directly on the wound. In addition, the pump should be inserted with its delivery portal first to minimize interaction between the delivered compound and the healing of the wound. Normally the incision heals within three days, and the animals show no sign of discomfort. Therefore, it is a useful alternative to repeated injections especially for rodents which are sensitive to frequent manipulation and are not well adapted to laboratory maintenance. This investigation also shows that recombinant murine IFNy is effective in L. striatus. The increasing cell counts in the spleen of IFN-y treated animals do not correspond with in vitro assays carried out in parallel, where the proliferation of spleen cells isolated from infected and naive animals was suppressed in the presence of IFN-y, even when stimulated with filarial antigen.Although there was no great effect on the course of the fila rial infection, some of the results suggest that cytokine work in this model should be continued. Encouraging results include the reduced leucocyte counts, the changes between the different types of leucocytes and the raised microfilaridermia. These results also support the...

UMF-078: A modified flubendazole with potent macrofilaricidal activity against Onchocerca ochengi in African cattle

“…There is little published information on the anthelminthic properties of the modified flubendazole, UMF-078, but it is has been shown to have both micro- and macrofilaricidal activity against Acanthocheilonema viteae and Litomosoides sigmodontis in jirds [ 15 ]. However, flubendazole itself has been studied quite extensively.…”