Cyclosporin A metabolites suppress T-cell proliferation by concanavalin A and in a mixed lymphocyte reaction

M. Abecassis, P. Y. Wong, N. Mason, F. Cheung, A. V. Mee, E. H. Cole, B. Langer, Z. Cohen, G. A. Levy

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

To ascertain if cyclosporine metabolites (CMs) have immunosuppressive activity, bile, whole blood and urine taken from patients after cholecystectomy and from a liver transplant recipient on cyclosporin A (CsA) were assayed to determine their effect on T-cell proliferation induced by concanavalin A (Con A) and in a two-way mixed-lymphocyte response. Bile and whole blood from the liver transplant patient completely suppressed Con A proliferation and the mixed lymphocyte response (MLR) at dilutions at which normal bile and whole bloode have no suppressive activity, but no such activity was noted from the urine. The CMs were separated into six peaks (fractions) by high-pressure liquid chromatography (HPLC). Metabolites were identified by internal standards and HPLC/mass spectrophometric analysis. Cyclosporine metabolite fractions 2 and 3 from bile and blood had immunosuppressive activity similar to parent CsA whereas fractions 5 and 6 demonstrated less but substantial immunosuppressive activity. Fractions 2, 3 and 5 demonstrated an ability to inhibit two-way MLR similar to parent CsA; the other metabolite fractions were able to inhibit the MLR but to a lesser extent. These results demonstrate that a number of CMs have immunosuppressive effects similar to those of the parent compound, and this may account for the lack of correlation between whole blood CsA levels and immunosuppressive activity.

Original languageEnglish (US)
Pages (from-to)145-150
Number of pages6
JournalCanadian Journal of Surgery
Volume31
Issue number3
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Surgery

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