USE OF INTRAVENOUS IMMUNOGLOBULIN TO DELAY XENOGENEIC HYPERACUTE REJECTION - IN-VIVO AND IN-VITRO EVALUATION

The delaying action of intravenous immunoglobulin (IVIG) from human origin on hyperacute xenogeneic rejection was assessed in the guinea pig-to-rat combination. IVIG (1500 mg/kg) injected i.v. into Lewis rats 1 hr before grafting significantly prolonged the mean guinea pig heart survival time (167 min, P<0.005) compared with control injections using NaCl (12 min) or the IVIG glycine vehicle (11 min). The effect of IVIG was also assessed in vitro in the pig-to-human combination. A dose-dependent inhibition of the complement-mediated direct cytotoxicity of human serum on pig RBC was shown using IVIG. The weak direct cytotoxicity of IVIG to pig RBC; which was abolished after preincubating IVIG with pig RBC, was attributed to the anti-pig xenoreactive natural antibodies (XNA) contained in the IVIG preparation. In vitro, XNA-depleted IVIG exerted a significantly stronger inhibitory effect than non-XNA-depleted IVIG, suggesting the use XNA-depleted IVIG in the pig-to-human combination. Although the mechanism of the inhibitory effect of IVIG remains to be clarified, IVIG may represent a new and simple therapeutic modality against xenogeneic hyperacute rejection.