On the Action of Cyclosporine A, Rapamycin and Tacrolimus on M. avium Including Subspecies paratuberculosisReportar como inadecuado




On the Action of Cyclosporine A, Rapamycin and Tacrolimus on M. avium Including Subspecies paratuberculosis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

Mycobacterium avium subspecies paratuberculosis MAP may be zoonotic. Recently the -immuno-modulators- methotrexate, azathioprine and 6-MP and the -anti-inflammatory- 5-ASA have been shown to inhibit MAP growth in vitro. We concluded that their most plausible mechanism of action is as antiMAP antibiotics. The -immunosuppressants- Cyclosporine A, Rapamycin and Tacrolimus FK 506 treat a variety of -autoimmune- and -inflammatory- diseases. Rapamycin and Tacrolimus are macrolides. We hypothesized that their mode of action may simply be to inhibit MAP growth.

Methodology

The effect on radiometric MAP 14CO2 growth kinetics of Cyclosporine A, Rapamycin and Tacrolimus on MAP cultured from humans Dominic and UCF 4 or ruminants ATCC 19698 and 303 and M. avium subspecies avium ATCC 25291 and 101 are presented as -percent decrease in cumulative GI- %-ΔcGI.

Principal Findings

The positive control clofazimine has 99%-ΔcGI at 0.5 µg-ml Dominic. Phthalimide, a negative control has no dose dependent inhibition on any strain. Against MAP there is dose dependent inhibition by the immunosuppressants. Cyclosporine has 97%-ΔcGI by 32 µg-ml Dominic, Rapamycin has 74%-ΔcGI by 64 µg-ml UCF 4 and Tacrolimus 43%-ΔcGI by 64 µg-ml UCF 4

Conclusions

We show heretofore-undescribed inhibition of MAP growth in vitro by -immunosuppressants;- the cyclic undecapeptide Cyclosporine A, and the macrolides Rapamycin and Tacrolimus. These data are compatible with our thesis that, unknowingly, the medical profession has been treating MAP infections since 1942 when 5-ASA and subsequently azathioprine, 6-MP and methotrexate were introduced in the therapy of some -autoimmune- and -inflammatory- diseases.



Autor: Robert J. Greenstein , Liya Su, Ramon A. Juste, Sheldon T. Brown

Fuente: http://plos.srce.hr/



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