Studies on the effect of systemic administration of sensitizers in guinea-pigs with contact sensitivity to inorganic metal compounds. 3. The effect of immunosuppressive agents on enhancing the unresponsiveness of already sensitized animals and an investigation of the action of the epicutaneous test within twenty-four hours

Abstract

Permanent specific immunological unresponsiveness can be produced in guinea-pigs already sensitive to K₂Cr₂O₇ by the combination of an intravenous injection of 20 mg/kg K₂Cr₂O₇ and an epicutaneous contact with K₂Cr₂O₇ within 24 hr; 2 mg/kg K₂Cr₂O₇ produces only temporary desensitization. Methotrexate and cyclophosphamide for 1 week at the time of the intravenous injection increased the intensity of the suppression but did not prolong the unresponsiveness. Anti-thymocyte serum alone had no effect. A combination of cyclophosphamide and anti-thymocyte serum for 1 week at the time of the intravenous injection prolonged the unresponsiveness for 2 months, but the animals regained sensitivity by 3 months. The addition of prednisolone to this combination, reduced the duration of unresponsiveness produced by a combination of the specific sensitizer, cyclophosphamide and anti-thymocyte serum.

In animals given 20 mg/kg K₂Cr₂O₇ intravenously, removal of the site of epicutaneous application of K₂Cr₂O₇ within 24 hr inhibits the development of specific unresponsiveness. Histological examination of the site of application of the sensitizer reveals microscopic evidence of an inflammatory reaction, although no macroscopic changes can be seen. These findings are discussed in the context of the mechanism of the production of specific immunological tolerance in animals already sensitive.