Inhibition of Graft-Vs-Host Induced Immunodeficiency with Immunosuppressive Therapy

Smith, Sidney R.; Pennline, Kenneth J.; Terminelli, Carol; DaFonseca, Manuel; Pellerito, Frances; Umland, Shelby P.

doi:10.3109/08923978809006455

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…It should also be noted that our findings correlate with previous results demonstrating highest S. mansoni worm burden reductions when artemether was administered three weeks after infection. 19,20 Cyclosporin A alone can induce the same level of protection to challenge infection, 21,22 but this effect might rather be due to immune modulation than a direct schistosomulocidal effect. This mechanism is unlikely with regard to artemether since it has not been seen thus far in any patient, 23 and we have never encountered it experimentally.…”

Section: Discussionmentioning

confidence: 99%

Triggering of High-Level Resistance Against Schistosoma Mansoni Reinfection by Artemether in the Mouse Model

Bergquist¹,

Utzinger²,

Chollet³

et al. 2004

The American Journal of Tropical Medicine and Hygiene

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Artemether, a methyl ether derivative of dihydroartemisinin, not only exhibits antimalarial properties, but also possesses strong activity against schistosomula, the immature stages of a parasitic worm that can cause schistosomiasis. To test if the effect would be similar to that of irradiation with respect to the induction of immunologic protective responses, groups of mice were infected with Schistosoma mansoni cercariae and treated with artemether at 1-3 weeks post-infection. Control mice were either infected with normal cercariae or with cercariae exposed to radiation that permitted early development but not maturation of the parasites. The mice were challenged six weeks after the initial infection, and the mean numbers of schistosomes recovered in the various groups were calculated upon dissection eight weeks post-challenge. The administration of artemether two weeks after the initial infection resulted in 58% protection, while giving the drug three weeks post-infection increased the level of protection to 81%. This level of protection is as high as that normally obtained by immunization with irradiated cercariae (84% in the present study) and is superior to the level of resistance obtained with any individual schistosome vaccine candidate antigen thus far reported.

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Section: Discussionmentioning

confidence: 99%

Triggering of High-Level Resistance Against Schistosoma Mansoni Reinfection by Artemether in the Mouse Model

Bergquist¹,

Utzinger²,

Chollet³

et al. 2004

The American Journal of Tropical Medicine and Hygiene

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Pharmacologic manipulation of graft versus host induced splenomegaly

Roudebush

Bryant

1992

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A murine graft versus host (GVH) model was developed as a tool for drug discovery. A pharmacological survey revealed that as a class the anti-rheumatics (e.g., auranofin, azathioprine, and methotrexate) were the most potent inhibitors of GVH induced splenomegaly. The immunosuppressants, cyclophosphamide and cyclosporine A, and the glucocorticoids (e.g., dexamethasone, hydrocortisone, and corticosterone) were all able to suppress the GVH response. Anti-inflammatory agents (e.g., indomethacin and piroxicam), and a series of central nervous system affecting drugs, including serotonin agonists (e.g., trifluromethylphenylpiperazine (tfMPP), 1-(3-chlorophenyl)piperazine (mCPP), and quipazine), and tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, and nortriptyline) typically were ineffective at doses up to 10 mg/kg. However, at high dose levels (30 mg/kg) piroxicam enhanced while amitriptyline and cyproheptadine (a mixed serotonin and histamine antagonist) suppressed GVH induced splenomegaly. These data provide a pharmacological profile for a series of immunomodulator, anti-inflammatory, and central nervous system active compounds in a classic immunologic model.

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