CYTOKINES IN RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN DA RATS - PERSISTENT MESSENGER-RNA EXPRESSION OF PROINFLAMMATORY CYTOKINES AND ABSENT EXPRESSION OF INTERLEUKIN-10 AND TRANSFORMING GROWTH-FACTOR-BETA

Experimental autoimmune encephalomyelitis (EAE) in rats is typically a brief and monophasic disease with sparse demyelination. However, inbr ed DA rats develop a demyelinating, prolonged and relapsing encephalom yelitis after immunization with rat spinal cord in incomplete Freund's adjuvant. This model enables studies of mechanisms related to chronic ity and demyelination, two hallmarks of multiple sclerosis (MS). Here we have investigated, in situ, the dynamics of cytokine mRNA expressio n in the central nervous system (CNS) and peripheral lymphoid organs ( lymph node cells and splenocytes) of diseased DA rats.-We demonstrate that peripheral lymphoid cells stimulated in vitro with encephalitogen ic peptides 69-87 and 87-101 of myelin basic protein responded with hi gh mRNA expression for proinflammatory cytokines; interferon-gamma, in terleukin-12 (IL-12), tumour necrosis factors alpha and beta, IL-1 bet a and cytolysin. A high expression of mRNA for these proinflammatory c ytokines was also observed in the CNS where it was accompanied by clas sical signs of inflammation such as expression of major histocompatibi lity complex class I and II, CD4, CD8 and IL-2 receptor. The expressio n of mRNA for proinflammatory cytokines was remarkably long-lasting in DA rats as compared to LEW rats which display a brief and monophasic EAE. Furthermore, mRNAs for putative immunodownmodulatory cytokines, i .e. transforming growth factor-beta (TGF-beta), IL-10 and IL-4 were al most absent in DA rats, in both the CNS and in vitro stimulated periph eral lymphoid cells, while their levels were elevated in the CNS of LE W rats during the recovery phase. We conclude that the MS-like prolong ed and relapsing EAE in DA rats is associated with a prolonged product ion of proinflammatory cytokines and/or low or absent production of im munodownmodulatory cytokines.