ANTITHYMOCYTE GLOBULIN PREPARATIONS AFTER HEART-TRANSPLANTATION - CYTOKINE RESPONSES IN-VIVO AND IN-VITRO

It is accepted that antithymocyte globulin (ATG) preparations vary in their bioactivity and side effects. However, this is poorly documented in the literature. We compared the clinical course and cytokine respo nse of heart transplant patients who had received either Merieux or St anford ATG preparations. The serum cytokine response (interleukin [IL] -6, tumor necrosis factor [TNF]-alpha, IL-4, and IL-10) of 28 consecut ive heart transplant recipients was measured for 14 days after surgery using ELISAs. The effect of various ATC; preparations on cytokine sti mulation of whole blood in vitro was also evaluated. There was a much greater in vivo IL-6 and TNF-alpha response to Merieux than to Stanfor d ATG (P<0.0005). There was little IL-4 or IL-10 response with either preparation. No side effects could be attributed to either treatment. No significant difference was seen in the frequency of rejection at 30 , 90, or 365 days. More infection episodes occurred in the group treat ed with Stanford ATG; at 30 days (0.5 compared with 0.2 episodes/patie nt; P=0.097), 90 days (1.2 compared with 0.5 episodes/patient; P=0.17) , and 365 days (2.8 compared with 1.8; P=0.59), although none of these differences were statistically significant. When tested in vitro for cytokine stimulation, the in vivo pattern was confirmed, with Merieux ATG producing greater levels of TNF-alpha and IL-6 than Stanford ATG. The differences in cytokine stimulation may be reflected in different immunosuppressive activities. Further research to elucidate the import ant components of immunosuppressive activity while excluding potential ly detrimental effects is important.