The effect of histamine on the induction of experimental autoimmune hemolytic anemia on OF1, BALB/c and SJL mice (1)
Histamine is a physiological agent well known to activate the suppression arm of the immune re- sponsein vitro. The experimental autoimmune hemolytic anemia (EAHA) induced by the injection of rat RBC into mice is a well-described model in which mice produce autoantibodes and anti-rat RBC hetero-antibodies. SJL mice are high responders in terms of auto-Ab and are not able to develop suppressor cells, and the majority of these mice die with an autoimmune hemolysis syndrome.
The percentage of animals showing a positive direct Coombs test one week after each injection reveals that those receiving 0.2-0.4 mg/g had a delayed incidence of the positive direct Coombs test. In contrast, the 0.1 mg/g dose of histamine did not reduce autoantibody production. The maximum inhibition by histamine was observed in the fourth week.
The histamine effect was abrogated when cimetidine (anti-H2) was injected 2 h before histamine. Diphenydramine (anti-H1) did not reduce autoantibody production.
Histamine did not inhibit the production of RBC autoantibodies in SJL strain. However, the mortality rate in the fourth week was the highest in this group (40%). Four out of ten mice died of anaphylactic shock.
There was no significant differ- ence in the rat anti-RBC antibody responses in these three strains. A slight suppression of hetero-antibody production was observed during the first 4 weeks, in comparison to mice not receiving histamine injections.
Using spleen cells from trinitrobenzene sulfonic acid-primed mice as regulators of the in vitro generation of primary anti-trinitrophenyl self-cytotoxic T-lymphocytes, showed that the H2 histamine receptor agonist tended to activate suppressor cell subsets allowing tolerance.