The balance between lymphatic and systemic absorption determines the outcome of sensitization for anaphylaxis in rats

Rats were sensitized to chicken ovalbumin or human gamma-globulin by inoculation without adjuvants into the peritoneal cavity in the healing phase of a chemical peritonitis. This phase is associated with striking enhancement of lymphatic absorption. Small doses of antigen sensitized the rats for subsequent induction of anaphylaxis, but large doses were almost completely ineffective (inverse dose-response relation). When certain adjuvants were added to the antigen, both high and low doses of antigen were effective sensitizers for anaphylaxis. Neither high nor low doses of antigen sensitized if injected without adjuvants into the unprepared peritoneal cavity or by any other route. The effects of sensitization with low or high doses of antigen and the results of inoculation by effective and ineffective routes were interpreted in terms of the balance between absorption into the lymphatics and into the systemic blood circulation. Supplemental antigen inoculated into the systemic circulation was able to tip the balance against sensitization even when sensitization was done with potent adjuvants and by a favorable route. Splenectomy had little or no effect on suppression by supplemental antigen.