on the action of cyclosporine a, rapamycin and tacrolimus on m. avium including subspecies paratuberculosis行动的环孢霉素a,雷帕霉素和他克莫司在m . avium包括亚种副结核.pdfVIP

On the Action of Cyclosporine A, Rapamycin and Tacrolimus on M. avium Including Subspecies paratuberculosis 1,2 2 4 3 Robert J. Greenstein *, Liya Su , Ramon A. Juste , Sheldon T. Brown 1 Department of Surgery, Veterans Affairs Medical Center (VAMC), Bronx, New York, United States of America, 2 Laboratory of Molecular Surgical Research, Veterans Affairs Medical Center (VAMC), Bronx, New York, United States of America, 3 Department of Medicine, Veterans Affairs Medical Center (VAMC), Bronx, New York, United States of America, 4 Institution Vasco de Investigation y Desarrollo Agrario Berreaga, Derio, Spain Abstract 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 UCF 4) or ruminants (ATCC 19698 303) and M. avium subspecies avium (ATCC 25291 101) are presented as ‘‘percent decrease in cumulative GI’’ (%-DcGI.) Principal Findings: The positive control clofazimine has 99%-DcGI at 0.5 mg/ml (Dominic). Phthalimide, a negative control has no dose dependent inhibition on any strain. Against MAP there is dose dependent inhibition by the immuno