Experimental eosinophilia; studies on the origin and relationship of tissue eosinophil cells to peripheral blood eosinophilia.

Abstract 1.1. A total of eighteen rabbits were given injections of erude beef liver extract by intramuscular, intraperitoneal, and intravenous routes in an attempt to induce an eosinophil cell response in peripheral blood, bone marrow, and splenic parenchyma. 2.2. Six of the animals received only crude beef liver extract for a six-week period. These developed a maximum rise in circulating blood eosinophils by the third week. 3.3. Six of the rabbits also received beef liver extract for a six-week period, but when a significant rise of circulating eosinophils had been reached by the third to fourth week, nitrogen mustard was administered intravenously and simultaneously with the liver extract during the remainder of the experimental period. The previously noted eosinophilia was then reversed to eosinopenic levels and was associated with leukopenia and lymphocytopenia. 4.4. Six of the animals received nitrogen mustard for two weeks prior to the injection of beef liver extract. This resulted in the development of peripheral blood cosinopenia and leukopenia. When cosinopenia had been established, the simultaneous administration of beef liver extract with nitrogen mustard failed to raise significantly the level of circulating eosinophils. 5.5. Crude beef liver extract adsorbed on aluminum hydroxide gel was injected intradermally into each animal at the start of the experiment, at the height of circulating cosinophilia, prior to the initial administration of nitrogen mustard, and at the conclusion of the course of parenteral beef liver extract injections. All locally injected skin sites were biopsied forty-eight hours following intradermal injections. 6.6. Infiltrations with eosinophilic granular cells were noted in the epidermis and corium of all animals, regardless of whether peripheral blood eosinophilia was present, had been reversed, or had been prevented from developing by the administration of nitrogen mustard. 7.7. Eosinophilic cellular infiltration into the splenic parenchyma was demonstrated microscopically in all rabbits to whom only beef liver extract was administered. In those who had also received nitrogen mustard, an absence of eosinophilic infiltration and the presence of atrophy of the lymphoid follicles were observed. 8.8. All animals treated with only beef liver extract exhibited marked hyperplastic granular eosinophilic bone marrows. Those who had been treated with nitrogen mustard prior to or simultaneously with liver extract exhibited agranular bone marrows with absence of eosinophilic precursor cells. 9.9. Precipitating antibodies to beef liver extract could not be demonstrated in the sera of all animals treated with this material. The development of cutaneous eosinophilic cellular infiltration could not be correlated with associated antibody response or antigen-antibody reaction. 10.10. Within the limitations of this experimental procedure, these results suggest that in the rabbit the development of a tissue eosinophilic cellular response may not be related to the presence of circulating peripheral blood eosinophils and local tissue eosinophils of the skin may have a source of origin independent of peripheral blood eosinophils. However, the exact origin or mode of their formation is not apparent.