Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor beta

J Neuroimmunol. 1995 Sep;61(2):205-12. doi: 10.1016/0165-5728(95)00100-g.

Abstract

The kinetics of mRNA expression in the central nervous system (CNS) for a series of putatively disease-promoting and disease-limiting cytokines during the course of experimental autoimmune encephalomyelitis (EAE) in Lewis rats were studied. Cytokine mRNA-expressing cells were detected in cryosections of spinal cords using in situ hybridization technique 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 appeared early and before onset of clinical signs of EAE; (ii) TNF-alpha peaked at height of clinical signs of EAE; (iii) IL-10 appeared increasingly at and after clinical recovery. The early expression of IL-12 prior to the expression of interferon-gamma (IFN-gamma) mRNA shown previously is consistent with a role of IL-12 in promoting proliferation and activation of T helper 1 (Th1) type cells producing IFN-gamma. The TNF-beta mRNA expression prior to onset of clinical signs favours a role for this cytokine in disease initiation. A pathogenic effector role of TNF-alpha was suggested from these observations that TNF-alpha mRNA expression roughly paralleled the clinical signs of EAE. This may be the case also for cytolysin. IL-10-expressing cells gradually increased to 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Gene Expression
  • In Situ Hybridization
  • Interleukin-10 / genetics*
  • Interleukin-12 / genetics*
  • Lymphotoxin-alpha / genetics*
  • Male
  • Membrane Glycoproteins / genetics*
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred Lew
  • Spinal Cord / metabolism*
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Lymphotoxin-alpha
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Perforin
  • Interleukin-10
  • Interleukin-12