Experimental hyperglobulinemia; the effect of injected ribonucleotide on serum globulin levels in rabbits undergoing immunization.
It was shown, by means of salt fractionation procedures and electrophoresis that a marked and sustained hyperglobulinemia regularly resulted when sodium ribonucleate was injected subcutaneously at frequent intervals into rabbits undergoing immunization with horse serum. The hyperglobulinemia was characterized by a large increase in the gamma globulin levels, and a slight increase in the alpha and beta globulin levels. In control experiments done concurrently, the immunization of rabbits with horse serum, accompanied by subcutaneous injections of saline instead of ribonucleate, resulted in only moderate elevations in gamma globulin levels, while injections of ribonucleate alone brought about slight elevations in all three globulin components in some of the animals. Precipitin tests showed that the rabbits immunized with horse serum and simultaneously treated with ribonucleate developed antibody titers against horse serum that were no higher than those of the immunized controls given saline instead of ribonucleate. Indeed, some of the animals treated with horse serum and ribonucleate had globulin levels that were much higher and had antibody titers that were significantly lower than were those of several rabbits receiving horse serum and saline. Injections of ribonucleate alone did not result in the formation of specific antibodies detectable by means of precipitin tests. The results made it plain that the hyperglobulinemia of the animals treated with horse serum and ribonucleate was not due to an excessive production of specific antibodies. The findings as a whole provide further evidence that nucleotides play an important role in the formation of proteins in animals, and they indicate that an abnormally increased utilization of ribonucleotides by cells capable of producing globulins may be a causative factor in the pathogenesis of hyperglobulinemia.