Humoral factor (s) in experimental hypersplenism.

I HE SYNDROME of hypersplenism is characterized by splenomegaly, selective or total blood cytopenias, normal or hyperplastic bone marrow, and disappearance of the cytopenias after splenectomy. The mechanism of the various forms of hypersplenism ( splenic thrombocytopenia, spenic anemia, splenic neutropenia, splenic pancytopenia ) is still under discussion. Clinical and experimental evidence has been presented in favor of two different hypotheses, the destruction of blood elements by sequestration in the spleen,1 and the inhibition of maturation and/or liberation of bone marrow cells by humoral mechanisms.2 Experimental hypersplenism has been produced by the injection of hydroxylamine,3 which is toxic for the reticuloendothelial system, by surgical ligation of the splenic and gastric coronary veins in the rabbit,4 by the administration of anti-bone marrow serum,a and by injecting macromolecular inert polymers such as polyvinyl alcohol or methylcellulose.6 The last method was shown by Palmer et al.7 to give more consistent results than the others : their animals developed splenomegaly, anemia, hyperplastic bone marrow, reticulocytosis, leukopenia and moderate thrombocytopenia, and the blood picture returned to normal after splenectomy. 1-listologic examination of spleen, liver, kidney and bone marrow revealed large and foamy macrophages, presumably containing the polymer. Using the methylcellubose type of experimental hypersplenism, Baldini8 was able to demonstrate that the anemia in the hypersplenic rat was not only due to increased hemolysis caused by engorgement of red cells in the enlarged spleen, but also to a defective bone marrow response to the anemia. Furthermore, by the lactating rat technic, the author could demonstrate the presence of humoral factor ( s ) in the milk of the hypersplenic animals. Rats born of normal mothers but fed from hypersplenic female rats developed anemia after 14 days of lactation, but normal baby rats fed from hypersplenic mothers splenectomized soon after partunition did not develop anemia. On the other hand, Giblett et al.,’1 working with methylcellulose-induced hypersplenism in adult rats studied the red cell survival, the phagocytic mass in the spleen and other indexes and concluded that the anemia was due to a combination of splenomegaly with resultant stasis and red cell destruction; bone marrow inhibition played no identifiable role in the pathogenesis of anemia. These two studies indicate that the mechanism of anemia in methycelluloseinduced hypersplenism in the rat is probably due to both humoral and sequestration factors. The present report describes a group of experiments dealing with the presence in the urine of methylcellulose-hypersplenic rats of a factor( s) capable of inducing anemia and thrombocytopenia when administered intraorally to the normal adult rat.