OPTIC NEURITIS IS ASSOCIATED WITH MYELIN BASIC-PROTEIN AND PROTEOLIPID PROTEIN REACTIVE CELLS PRODUCING INTERFERON-GAMMA, INTERLEUKIN-4 ANDTRANSFORMING GROWTH-FACTOR-BETA

Studies on patients with monosymptomatic optic neuritis (ON) should gi ve opportunities to identify features typical for early multiple scler osis (MS). There are increased T and B cell responses to the myelin co mponents myelin basic protein (MBP) and proteolipid protein (PLP) in b oth ON and MS, but there is little information on the types of cytokin es produced by such cells. We describe the use of in situ hybridizatio n with complementary DNA oligonucleotide probes to detect and enumerat e mononuclear cells expressing mRNA for the cytokines interferon-gamma (IFN-gamma) which augments cell-mediated immunity; interleukin-4 (IL- 4) which promotes the B cell response; and transforming growth factor beta (TGF-beta) that in many cases downregulates immune responses. Exp ression of these cytokines was studied in mononuclear cells from perip heral blood and cerebrospinal fluid (CSF) from patients with ON and MS after in vitro exposure to MBP and PLP, and in absence of antigen. Th ere were elevated levels of cells that in response to MBP and PLP expr essed IFN-gamma, IL-4 and TGF-beta mRNA in blood and further enriched in CSF in both ON and MS, compared to patients with other neurological diseases. The results suggest that IFN-gamma, IL-4 as well as TGF-bet a are involved in both ON and MS, and that the cytokine profile in ear ly MS as reflected by ON is not different from that in clinically defi nite MS.