Cyclosporin A prevents suppression of delayed-type hypersensitivity in mice immunized with high-dose sheep erythrocytes.
When administered intraperitoneally to mice 2 days before immunization with a tolerogenic dose (10(9)) of sheep red blood cells (SRBC), cyclosporin A (CsA; 200 mg/kg) strikingly augmented 4-day delayed-type hypersensitivity (DTH) footpad reactions. These enhanced responses were similar in magnitude to those seen in animals sensitized with an immunogenic, low-dose (10(6)) SRBC. The stimulatory effect of CsA was observed over the dose range of 5-200 mg/kg and was obtained in animals given the drug in one injection, up to 7 days before sensitization. The augmentation of DTH was characterized by footpad swelling, intense mononuclear cell infiltration and increased deposition of 125I-fibrinogen within the challenge site. In addition, increased expression of procoagulant activity by spleen cells in response to antigen was observed. Cell transfer experiments showed that the CsA-enhanced DTH could be adoptively transferred to naive recipients. Additional transfers conducted at the time of antigen challenge suggested that, under the conditions described, CsA inhibited the action of a population of suppressor cells normally effective during DTH reactions.
D000818:Animals; D001779:Blood Coagulation Factors / Q000032:analysis; D003524:Cyclosporins / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000276:immunology*; D005340:Fibrinogen / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects*; D007116:Immunization, Passive; D051379:Mice; D008815:Mice, Inbred Strains; D012756:Sheep
D001779:Blood Coagulation Factors; D003524:Cyclosporins; C045071:leukocyte procoagulant activity; D005340:Fibrinogen