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    Effects of Salmeterol on host resistance to Trichinella spiralis in rats

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    Authors
    van Loveren H
    de Jong WH
    van der Stappen AJ
    Verlaan AJM
    de Waal EJ
    Type
    Report
    Language
    en
    
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    Title
    Effects of Salmeterol on host resistance to Trichinella spiralis in rats
    Translated Title
    Invloed van Salmeterol op weerstand tegen Trichinella spiralis
    Publiekssamenvatting
    Salmeterol is een lang werkende Beta2-adrenoreceptor agonist. In het verleden is dit geneesmiddel getest voor immunotoxiciteit in een herhaalde dosis toxiciteitsstudie gedurende 28 dagen in de rat. In deze Tier I studie, waren de serum IgG spiegels verhoogd bij doseringen van 2 en 10 mg/kg/dag. Thans is salmeterol onderzocht in een Tier II immuunfunctie test met betrekking tot de weerstand tegen infectie met Trichinella spiralis parasieten. Ratten werden dagelijks behandeld met 0, 2, 6 en 10 mg/kg/dag salmeterol gedurende 28 dagen. Op dag 29 werden de dieren met Trichinella spiralis parasieten geinfecteerd. Zes weken na het begin van de infectie werd de weerstand geevalueerd. Het aantal Trichinella spiralis spierlarven en de ontstekingsreacties rond ingekapselde larven in de tong werden niet door de salmeterol behandeling beinvloed. Ook was de opbrengst van spierlarven in het hele karkas onveranderd. De IgM, IgA en IgE antilichaamrespons tegen Trichinella spiralis liet geen effect zien. Alleen bij de hoogst onderzochte dosering was de anti-Trichinella spiralis IgG antilichaamrespons onderdrukt. Het effect van salmeterol op de anti-Trichinella spiralis antlichaamvorming had echter klaarblijkelijk geen negatieve invloed op het vermogen van de dieren om de infectie met succes het hoofd te bieden.<br>
    Salmeterol is a long-acting Beta2-adrenoreceptor agonist. The compound has previously been screened for immunotoxic potential in a Tier I repeated dose toxicity study in rats for 28 days. The total serum IgG levels were increased at dose levels of 2 and 10 mg/kg/day. Presently, salmeterol was studied in a Tier II immune function assay addressing the host resistance to Trichinella spiralis parasites. Rats were daily treated with salmeterol for 28 days at dose levels of 0, 2, 6 and 10 mg/kg/day. On day 29, the animals were infected with Trichinella spiralis parasites. After six weeks, host resistance was examined. The numbers of Trichinella spiralis muscle larvae in the tongue nor the inflammatory reactions around the encapsulated larvae were affected by salmeterol treatment. The yield of muscle larvae in the whole carcass was not changed either. The IgM, IgA and IgE antibody responses to Trichinella spiralis were unaffected. Only at the highest dose level tested, the anti-Trichinella spiralis IgG antibody response was decreased significantly. However, salmeterol's interference with the generation of anti-Trichinella spiralis antibodies of the IgG subclass apparently did not adversely affect the successful resistance of the animals against the infection.<br>
    Publisher
    Rijksinstituut voor Volksgezondheid en Milieu RIVM
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