In Vitro Cytokine Responses in Liver Transplant Recipients Treated with Cyclosporine A and Tacrolimus

The inhibitory effect of Cyclosporine A (CsA) and Tacrolimus (Tacr) on interleukin 2 (IL-2) are well known, and the importance of Th1-type (IL-2, interferon gamma), and Th2-type (IL-4, IL-6, and IL-10) cytokine secretion in preventing allograft rejection is a controversial issue. The immunological mechanisms involved in long-term liver transplant recipients under CsA and Tacr were not studied precisely. This study was designed to evaluate the effects of CsA and Tacr on the immune response of 62 long-term survivors following liver transplantation. T-cell and B-cell subpopulations, the T helper (Th) cell activity, T-cell cytokine production, Staphylococcus aureus Cowan strain I (SAC-I)-stimulated B-cell responses and PWM-stimulated B-cell responses were examined. CsA and Tacr decreased whole T-cell populations as well as CD4+T-cell IL-2 responses (p < 0.005, Tacr and p = 0.02, CsA), impaired CD4+ cell Th activity (p < 0.01, Tacr and p = 0.02, CsA) and reduced SAC-I-stimulated B-cell responses (immunoglobulin-secreting cells [ISC]: p = 0.001, Tacr and p < 0.05, CsA). A significantly impaired T-cell IL-10 secretion (p = 0.0001) and decreased Th function of whole T cells was found in Tacr-treated patients only, whereas unstimulated Th1 responses and SAC-I-stimulated B-cell IL-6 responses were reduced in CsA-treated patients. Our data show that Tacr suppresses T-, CD4+-, and B-cell responses more effectively than CsA which may be relevant in the maintenance of long-term stable liver graft function.