The effects of drugs on worm expulsion in theNippostrongylus brasiliensisinfected rat: a discussion of the interpretation of drug action

Abstract

In rats treated with compound 48/80 or histamine, worm expulsion was inhibited. Treatment with a histidine decarboxylase inhibitor accelerated worm expulsion. Treatment with compound 48/80 elevates histamine and histidine decarboxylase levels and reduces circulating reagin titres. These results show that histamine is not responsible for worm expulsion.Compounds such as isoprenaline and theophylline which increase cellular levels of cyclic 3′,5-AMP, prevented worm expulsion.It is concluded that the evidence that amines are involved in worm expulsion needs reassessing and that cellular release mechanisms in general may be affected by drugs thought to act solely on amine release. In particular, the release of effector substances from sensitized lymphocytes on contact with antigen may be affected by these treatments.The skilful technical assistance of Miss R. Keist and Miss I. Beeger is gratefully acknowledged. We thank Mr H. Berchtold, Biostatistisches Zentrum der Universität Zürich, for the statistical evaluation of the data.

Studies on the Role of Histamine and 5-Hydroxytryptamine in Immunity against the Nematode <i>Trichostongylus colubriformis</i>

“…These studies led to the suggestion that the amines participate in the immune response against T. colubriformis, and that basophils, therefore, function as effec tor cells carrying histamine to, and releasing it at the site of infection. Similar studies in other host-parasite systems, notably in rats infected with Nippostrongylus brasiliensis have also led to the suggestion that the amines are involved in nematode rejection [Urquhart et al, 1965;Jarrett et al, 1967], However, Keller and Ogilvie [1972] and Kelly and Dineen [1972] have pointed out that caution is needed in interpretation of the results of experiments in which drugs are used to inhibit worm expulsion. In addi tion, because histamine levels in the whole small intestine of rats during a primary infection with N. brasiliensis were lower than in uninfected con trols, Keller [1971] concluded histamine was not involved in rejection of the nematode.…”

Rôle de l’inflammation dans le déparasitage spontané deStrongyloides ratti

“…que nous avons obtenu par des traitements au maléate de dexchlorphéniramine (antihistaminique) et à la cyproheptadine (antisérotonine et antihistaminique) rejoint les résultats obtenus avec la cyproheptadine (Keller et Ogilvie, 1972), la mépyramine (Urquhart et Mulli gan, 1965 ;Keller et Ogilvie, 1972), ou l'acide lysergique (Urquhart et Mulligan, 1965).…”

Studies on the Inhibition of Rapid Expulsion of <i>Trichinella spiralis </i>in Rats

“…The involvement of immediate hypersensitivity or of prostaglandins in the process of worm expulsion from the intestine has been a long-standing theme of immunoparasitology [8,II,[13][14][15][16][19][20][21], Of all the processes of worm eviction, RE is perhaps the most likely candidate for an immediate hypersen sitivity-mediated event. Rejection in RF.-primed rats begins within hours of worm invasion and the re sponse is largely completed in 8-12 h (fig.…”

“…Three ma jor restrictions apply to the interpretation of experi ments where role is deduced from functional inhibi tion studies of any potential mediator. The first of these was discussed by Keller and Ogilvie [14] who cautioned against overinterpretation of data based on long-term administration of drugs with multiple phy siological effects. The second problem arises in deter mining whether the administered inhibitor has func tioned at the time and the site required to depress the parameter that is under investigation.…”