Severe systemic vascular necrosis in cyclosporin-treated rabbits with acute serum sickness

Rabbits given acute serum sickness (ASS) and treated with cyclosporin A (CyA) developed a severe, systemic vascular injury, which was not similar to that normally seen in ASS. Thirty-three NZW rabbits received a single intravenous injection of 250 mg/kg bovine serum albumen (BSA) with or without endotoxin (5 micrograms/kg), on day 0. Groups of rabbits were given intramuscular CyA as follows: 15 mg/kg/day from day -2 to +8, or 25 mg/kg/day from day -2 to +3 or day 0 to 5. Muscular arteries of the heart and splanchnic organs developed an arterial injury in which there was extensive fibrinoid necrosis of the vessel wall but little or none of the mononuclear cell reaction that is normally associated with the arteritis of ASS. A microvascular injury also occurred which led to interstitial haemorrhage in the gastric mucosa and multi-focal necrosis in the heart and liver. These lesions were seen with equal frequency in all groups of rabbits with serum sickness who received CyA, irrespective of whether they also received endotoxin. We suggest that CyA altered the host inflammatory response to the injury initiated by the BSA-anti-BSA immune complexes and this led to enhanced vascular injury. The inhibition by CyA of the perivascular cellular reaction suggests that this reaction may be mediated by T lymphocytes. This model should provide further insight into the pathogenesis of arteritis, as well as the mechanisms of cyclosporin toxicity.