Cyclosporin A treatment modulates cytokine mRNA expression by inflammatorycells extracted from the spinal cord of rats with experimental autoimmune encephalomyelitis induced by inoculation with myelin basic protein

In Lewis rats, treatment with high doses of cyclosporin A (CsA) suppresses clinical signs of experimental autoimmune encephalomyelitis (EAE), although disease occurs when treatment is ceased. Treatment with low doses of CsA c auses EAE to take a chronic relapsing course. We have previously shown that CsA treatment causes a decline in the number of T cells and increased infl ammatory cell apoptosis in the spinal cord. The present study was undertake n to assess whether CsA therapy also modulates cytokine mRNA expression by inflammatory cells in the spinal cord of rats with EAE, looking for changes that might contribute to the observed effects of CsA on the course of EAE. EAE was induced in Lewis rats by inoculation with myelin basic protein and adjuvants. At the peak of neurological signs, on day 14 after inoculation, rats were given a single intraperitoneal injection of saline, or CsA at a dose of 8, 16, 32 or 64 mg/kg. The next day, rats were sacrificed, the spin al cords removed, inflammatory cells were extracted from the cords, and mRN A isolated from these cells. Expression of cytokine mRNA was assessed by se mi-quantitative reverse transcription polymerase chain reaction (PCR) and b y quantitative real-time PCR. With both techniques, we found that CsA suppr essed the expression of interferon-gamma mRNA and interleukin-2 (IL-2) mRNA . With real-time PCR, we found that CsA caused significantly increased expr ession of transforming growth factor-beta mRNA. With the different techniqu es, we observed no consistent pattern of alteration of expression of interl eukin-10 or interleukin-4 mRNA. It is possible that these changes in cytoki ne mRNA expression contribute to the modulation of the clinical course of E AE that is produced by CsA treatment. (C) 2001 Elsevier Science B.V. All ri ghts reserved.