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Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug

Published online by Cambridge University Press:  06 April 2009

R. M. Maizels  and
D. A. Denham
R. M. Maizels
Affiliation:
Wellcome Research Centre for Parasitic Infections, Department of Biology, Imperial College of Science, Technology and Medicine, Prince Consort Road, London SW7 2BB, UK
D. A. Denham
Affiliation:
London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT
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Summary

Anti-parasitic drugs may achieve their therapeutic effect either by direct activity against the pathogenic organism, or by altering host factors which lead to parasite killing. In this review, we discuss the evidence for an indirect mode of action for one major anti-filarial drug, diethylcarbamazine (DEC). The interpretation most consistent with existing data is that DEC alters arachidonic acid metabolism in microfilariae and in host endothelial cells. These changes may result in vasoconstriction and amplified endothelial adhesion leading to immobilization of microfilarial parasites, enhanced adherence and cytotoxic activity by host platelets and granulocytes. These events would represent activation of the innate, non-specific immune system, independent of the adaptive, antigen-specific, immune response. This model explains the paradox between rapid clearance in vivo and the lack of an in vitro effect, as well as the efficacy of DEC in non-immune animals.

Keywords

adhesionanthelminticsarachidonic acideosinophilsfilariasisfilaricideshelminthotoxicityleukotrienesmicrofilaricideneutrophilsplateletsprostanoids
Type
Research Article
Information
Parasitology , Volume 105 , Issue S1: Chemotherapy and the immune system , January 1992 , pp. S49 - S60
Copyright
Copyright © Cambridge University Press 1992

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