CYTOKINE PRODUCTION IN THE CENTRAL-NERVOUS-SYSTEM OF LEWIS RATS WITH EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - DYNAMICS OF MESSENGER-RNA EXPRESSION FOR INTERLEUKIN-10, INTERLEUKIN-12, CYTOLYSIN, TUMOR-NECROSIS-FACTOR-ALPHA AND TUMOR-NECROSIS-FACTOR-BETA

The kinetics of mRNA expression in the central nervous system (CNS) fo r a series of putatively disease-promoting and disease-limiting cytoki nes during the course of experimental autoimmune encephalomyelitis (EA E) in Lewis rats were studied. Cytokine mRNA-expressing cells were det ected in cryosections of spinal cords using in situ hybridization tech nique with synthetic oligonucleotide probes, Three stages of cytokine mRNA expression could be distinguished: (i) interleukin (IL)-12, tumor necrosis factor (TNF)-beta (=lymphotoxin-alpha) and cytolysin appeare d early and before onset of clinical signs of EAE; (ii) TNF-alpha peak ed at height of clinical signs of EAE; (iii) IL-10 appeared increasing ly at and after clinical recovery. The early expression of IL-12 prior to the expression of interferon-gamma (IFN-gamma) mRNA shown previous ly is consistent with a role of IL-12 in promoting proliferation and a ctivation of T helper 1 (Th1) type cells producing IFN-gamma. The TNF- beta mRNA expression prior to onset of clinical signs favours a role f or this cytokine in disease initiation. A pathogenic effector role of TNF-alpha was suggested from these observations that TNF-alpha mRNA ex pression roughly paralleled the clinical signs of EAE. This may be the case also for cytolysin. IL-10-expressing cells gradually increased t o high levels in the recovery phase of EAE, consistent with a function in down-regulating the CNS inflammation. From these data we conclude that there is an ordered appearance of putative disease-promoting and -limiting cytokines in the CNS during acute monophasic EAE.