Action of cyclosporin A on the tapeworms<i>Hymenolepis microstoma, H. diminuta</i>and<i>Mesocestoides corti in vivo</i>

Chappell, L. H.; Wastling, Jonathan M.; Hurd, Hilary

doi:10.1017/s0031182000062211

Cited by 18 publications

(20 citation statements)

References 31 publications

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“…E/S products from N. brasiliensis and Ascaris suum are resistant to rMCP-I (from rat connective tissue mast cells) and to rMCP-II (from rat IMMC) (Qureshi et al 1987) but internal cuticular collagens from Necator americanus are degraded by rMCP-II (McKean & Pritchard 1989). The biomass of H. microstoma decreased immediately following administration of CsA but, as demonstrated elsewhere (Chappell et al 1989), rose again after drug withdrawal. Here CsA had no effect on mucosal mastocytosis and mMCP-I concentration in the intestine, bile duct or serum since the drug dose was essentially nonimmunosuppressive.…”

Section: Discussionsupporting

confidence: 56%

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Mucosal mast cell responses and release of mast cell protease‐I in infections of mice with Hymenolepis diminuta and H. microstoma: modulation by cyclosporin A

McLauchlan

Roberts

Loxton

et al. 1999

Parasite Immunology

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The dynamics of intestinal mucosal mast cells and the major mucosal mast cell protease were followed during the course of laboratory infections of mice with Hymenolepis diminuta and H. microstoma. The effects of the drug cyclosporin A (CsA), which is both immunosuppressive and selectively anthelmintic depending upon dose regime, were determined. In H. diminuta infections worm expulsion occurred around day 9 and coincided with peak mastocytosis and peak mMCP-I concentrations in tissues and serum. Immunosuppressive treatment with CsA prevented worm expulsion, permitting some individuals to reach maturity, and abrogated mast cell proliferation and mMCP-I production and release. By contrast, H. microstoma infections persisted for 64 days in spite of a considerable mastocyosis in both intestine and bile duct tissues accompanied by a high level of mMCP-I in tissues and serum. A subimmunosuppressive regime of CsA had only limited effects on worms and mast cell numbers and activity. Together these data shed light on the variable mast cell response to gastrointestinal infections and on the potential significance of parasite location in evasion of mast cell action. Use of CsA reveals the contributions of both T cell-dependent mechanisms, including mast cell proliferation and activation, and T cell-independent events in regulating intestinal helminth infections.

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Section: Discussionsupporting

confidence: 56%

“…CsA is not toxic to H. diminuta in vivo or in vitro (Chappell et al 1989, Wastling et el. 1990) and immunosuppressive doses allow > 90% of worms to survive to maturity in mice, delaying but not completely abrogating worm expulsion (Wastling et al 1990, present study).…”

Section: Discussionmentioning

confidence: 95%

Mucosal mast cell responses and release of mast cell protease‐I in infections of mice with Hymenolepis diminuta and H. microstoma: modulation by cyclosporin A

McLauchlan

Roberts

Loxton

et al. 1999

Parasite Immunology

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“…The structural integrity of the worm is ultimately compromised by surface damage around the dorsal tubercles or the protrusion of the gut through the tegument (Munro & McLaren 1990a, Millership 1995. However, it seems unlikely that the gut is the primary target for CsA since the drug is active against cestodes which lack an alimentary canal (Chappell, Wastling & Hurd 1989). This study offers further evidence of the involvement of the immune system with drug action using CsA, a drug which is both immunosuppressive and selectively antiparasitic.…”

Section: Discussionmentioning

confidence: 70%

“…For instance, Munro et al (1991) showed that CsA treatment severely limits the migration of recently penetrated schistosomula; it is possible that these immobilized larvae are killed by immune effectors but there is currently no firm evidence to support this contention. What remains to be explained, therefore, is why CsA is selectively toxic and fails to damage the tegument of certain helminth parasites such as Hymenolepis diminuta (Chappell, Wastling & Hurd 1989). Recent studies suggest that cyclophilins are present in parasites and these may be the endogenous targets for the action of CsA (Roberts, Sternberg & Chappell 1995) although further data are required before such proposals can be substantiated.…”

Section: Discussionmentioning

confidence: 99%

Synergistic action of cyclosporin A and polyspecific rabbit anti‐sera against murine Schistosoma mansoni

Millership

Chappell

Fallon

1996

Parasite Immunology

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The efficacy of cyclosporin A (CsA) treatment against Schistosoma mansoni in mice was compared with treatments that included co-administration of one of two anti-sera (infected rabbit serum (IRS) obtained by repeated infection and a worm membrane antigen anti-serum (WSS) obtained by immunization with worm surface supernatants). These two sera recognized a number of worm antigens but differed in precise detail. Administration of CsA alone to mice harbouring mature infections of S. mansoni reduced worm burdens and preferentially targeted female worms. Sera administered alone had no effect on worm burdens. Co-administration of worm membrane antigen anti-serum (WSS) with CsA reduced worm burden significantly compared with drug treatment alone. Male worms were more susceptible to this combined treatment regime. Anti-infection serum (IRS) had a lesser stimulatory activity in combination with CsA which was not statistically different from the effects of CsA alone on worm burdens. The data suggest that CsA-induced surface damage to the parasite may reveal specific antigens that were previously unavailable for host attack.

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“…This is in contrast to other cestode larvae, against which mebendazole exerts a parasitostatic effect only. Deleterious actions of other drugs on Mesocestoides tetrathyridia, including cyclosporin A (Chappell et al 1989) and albendazole (Terenina et al 1998), have also been reported.…”

Section: Relevance Of Echinococcus Metacestode Screening Models For Omentioning

confidence: 99%

Echinococcusmetacestodes as laboratory models for the screening of drugs against cestodes and trematodes

Hemphill¹,

Lundström‐Stadelmann²,

Scholl³

et al. 2009

Parasitology

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Among the cestodes, Echinococcus granulosus, Echinococcus multilocularis and Taenia solium represent the most dangerous parasites. Their larval stages cause the diseases cystic echinococcosis (CE), alveolar echincoccosis (AE) and cysticercosis, respectively, which exhibit considerable medical and veterinary health concerns with a profound economic impact. Others caused by other cestodes, such as species of the genera Mesocestoides and Hymenolepis, are relatively rare in humans. In this review, we will focus on E. granulosus and E. multilocularis metacestode laboratory models and will review the use of these models in the search for novel drugs that could be employed for chemotherapeutic treatment of echinococcosis. Clearly, improved therapeutic drugs are needed for the treatment of AE and CE, and this can only be achieved through the development of medium-to-high throughput screening approaches. The most recent achievements in the in vitro culture and genetic manipulation of E. multilocularis cells and metacestodes, and the accessability of the E. multilocularis genome and EST sequence information, have rendered the E. multilocularis model uniquely suited for studies on drug-efficacy and drug target identification. This could lead to the development of novel compounds for the use in chemotherapy against echinococcosis, and possibly against diseases caused by other cestodes, and potentially also trematodes.

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Action of cyclosporin A on the tapewormsHymenolepis microstoma, H. diminutaandMesocestoides corti in vivo

Cited by 18 publications

References 31 publications

Mucosal mast cell responses and release of mast cell protease‐I in infections of mice with Hymenolepis diminuta and H. microstoma: modulation by cyclosporin A

Mucosal mast cell responses and release of mast cell protease‐I in infections of mice with Hymenolepis diminuta and H. microstoma: modulation by cyclosporin A

Synergistic action of cyclosporin A and polyspecific rabbit anti‐sera against murine Schistosoma mansoni

Echinococcusmetacestodes as laboratory models for the screening of drugs against cestodes and trematodes

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