Myelin/axonal pathology in interleukin-12 induced serial relapses of experimental allergic encephalomyelitis in the Lewis rat

Lewis rats, on recovery from monophasic clinical experimental allergic ence phalomyelitis (EAE), can be induced to develop repeated paralytic relapses with a graded reduction in clinical severity following intraperitoneal admi nistration of IL-12. By the time of the third relapse, the number and size of inflammatory cuffs in the spinal cord were reduced with the makeup of th e cellular infiltrate shifting to a significantly increased number of B cel ls. Serum levels of myelin basic protein (MBP)-specific IgG1 and IgG2b were found to rise over time while MBP and MBP peptide-positive macrophages and microglia became evident in perivascular cuffs and in spinal cord parenchy ma, indicative of myelin phagocytosis. Axonal death was observed in semithi n and EM sections of spinal cord in third relapse animals in association wi th iNOS and tPA immunostaining throughout gray and white matter. These neur otoxic or excitotoxic agents may contribute to axonal damage directly or in directly by activated microglia and macrophages, leading to Limited damage of the axonal-myelin unit.