Changes in immunological parameters after conversion from cyclosporine A to azathioprine in renal transplant recipients

Abstract

Long term CsA therapy did not interfere with the basal levels of natural killer (NK) activity in stable cadaveric renal transplant recipients. However, 3 months after changing immunosuppressive therapy from CsA to AZA, NK activity was significantly decreased (36 +/- 25% vs 19 +/- 15%, P less than 0.01). Following in vitro exposure to IFN-gamma an increase in NK activity from 36 to 44% (P less than 0.05) could be induced during CsA therapy but this was no longer observed after conversion to AZA (19 to 22%, N.S.). A prominent decline in the number of NK cells expressing the surface receptor for the Fc portion of IgG was also found postconversion. The IFN-gamma production capacity after mitogen stimulation of unprimed lymphocytes was more depressed during CsA than during AZA therapy (median 25 vs 80 U/ml 10(6) cells, P less than 0.05), suggesting a reversible inhibition of CsA on lymphokine production. Despite the better IFN-gamma production capacity, both the activity, inducibility and number of NK cells were significantly lower under AZA therapy than under CsA therapy. These findings indicate that CsA exerts its immunosuppressive action without an important interference with NK activity. Monitoring mononuclear cells showed a decrease in absolute numbers of all phenotypically distinct cells studied after conversion. The prominent decrease in CD 8 cells resulted in an increase of CD 4/CD 8 ratio.