The effects of deoxyspergualin on lymphocytes and monocytes in vivo and in vitro.

It has been suggested that deoxyspergualin, a new immunosuppressant, may be immunosuppressive via a purely antimonocyte action. As this appears to be unlikely, this study examines the effect of deoxyspergualin on lymphocyte and monocyte function in vivo and in vitro. It is demonstrated that deoxyspergualin inhibits human lymphocyte proliferation in response to mitogens and allogeneic stimulation. Furthermore, it is demonstrated that this inhibition occurs no matter whether the monocytes or lymphocytes are treated with the drug. The drug appears to have a more significant effect on the lymphocyte component; rhIL-2 appears partly to overcome the deoxyspergualin-induced inhibition of lymphocyte proliferation in response to allogeneic stimulation. In a rat renal transplant model, deoxyspergualin-treated animals demonstrated a moderate interstitial infiltrate in their transplant kidneys that comprised approximately 50% each of macrophages and lymphocytes. There was significantly less activation (e.g. IL-2R expression) in the treated kidney infiltrates compared to rejected controls. Thus deoxyspergualin is an agent with immunosuppressive effects on both lymphocytes and monocytes and would appear to have more marked effects on lymphocytes.