Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids.

Kreek

Pender

1990

Experimental allergic neuritis (EAN) was induced in Lewis rats by inoculation with bovine intradural root myelin plus adjuvants. Animals treated with high dose (30 mg/kg) cyclosporin A (CsA) 3 times per week did not develop clinical EAN during the period of CsA treatment, but had an episode of EAN after cessation of CsA treatment. Animals treated with low dose (4 mg/kg) CsA 3 times per week developed EAN during the period of treatment, and after cessation of CsA treatment all of these animals developed relapsing EAN with disease continuing for up to four episodes. In contrast, 30-40% of untreated animals had a mild second episode of EAN but no further attacks. Histological studies performed in treated and untreated animals at the time of clinical episodes revealed inflammation and demyelination in the spinal roots and dorsal root ganglia. When animals were challenged with a second inoculation at age 7 months, one of 15 untreated control animals but none of the CsA treated animals developed an episode of EAN.

Section: Discussionsupporting

confidence: 87%

The effects of prophylactic cyclosporin A on experimental allergic neuritis (EAN) in the Lewis rat. Induction of relapsing EAN using low dose cyclosporin A

Kreek

Pender

1990

“…The increased relative expression of cytokines during late clinical recovery could also reflect an influx of activated T cells from the periphery. An influx of activated T cells could occur after a waning in the effects of endogenous corticosteroids which have a role in clinical recovery from EAE (MacPhee et al, 1989) and which may act by reducing influx of cells into the CNS.…”

Section: Discussionmentioning

confidence: 99%

Cytokine expression by inflammatory cells obtained from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis induced by inoculation with myelin basic protein and adjuvants

Nickson

Pender

1998

Inflammatory cells were obtained from the spinal cords of rats with acute experimental autoimmune encephalomyelitis EAE induced by inoculation with myelin basic protein MBP and adjuvants. Reverse transcriptase-polymerase chain reaction RT-PCR was used to investigate the expression of mRNA for interleukin-2 IL-2 , IL-4, IL-10 and interferon-γ (IFN-γ) by cells from groups of rats studied 10-21 days after inoculation. On all days of study, the inflammatory cells, which were predominantly lymphocytes, expressed mRNA for IL-2, IL-4, IL-10 and IFN-γ. In the mRNA from normal rat spinal cord tissue, there was little expression of cytokine mRNA. Cells from a short-term MBP-reactive T cell line expressed all the cytokines. Densitometry was used to measure the products of PCR, to assess the expression of each cytokine relative to that of β-actin. IL-2 mRNA was expressed throughout the course of disease and reached a peak on day 18, during late clinical recovery. IFN-γ was expressed throughout the course of the disease and was also high during late recovery. IL-4 mRNA was present in the spinal cord throughout the course of the disease, with a slight rise during late recovery. Relative expression of IL-10 rose to a peak on days 17-19, during late recovery from clinical disease. This study indicates that IL-2, IL-4, IL-10 and IFN-γ are expressed by inflammatory cells in the spinal cord in EAE, with the relative expression of all cytokines being high during late clinical recovery.

“…Endogenous corticosteroid production is thought to be important in spontaneous recovery from EAE (Levine et al, 1980;MacPhee et al, 1989). Therapy with exogenous corticosteroids has also been shown to be of clinical benefit in EAE (Kibler, 1965;Vogel et al, 1972).…”

Section: Discussionmentioning

confidence: 99%

Corticosteroid treatment of experimental autoimmune encephalomyelitis in the Lewis rat results in loss of Vβ8.2+ and myelin basic protein-reactive cells from the spinal cord, with increased total T-cell apoptosis but reduced apoptosis of Vβ8.2+ cells

Nickson

Tabi

et al. 1996

We have studied the effects of corticosteroid treatment on the numbers of lymphocytes obtained from the spinal cords of Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants. Flow cytometric studies showed that treatment with dexamethasone (4 mg/kg) 8-12 h prior to study on day 14 after inoculation resulted in a reduction in the numbers of CD5 + , TCR + and V 8.2 + cells in the spinal cord. Limiting dilution analysis indicated that dexamethasone treatment 12 h prior to study on day 12 after inoculation reduced the frequencies of MBP-reactive and interleukin-2-responsive lymphocytes in the spinal cord to low levels, but reduced the frequency of concanavalin-A-responsive lymphocytes to a lesser extent. Using propidium iodide staining of nuclear chromatin we also studied lymphocyte apoptosis. Greater numbers of apoptotic cells were found in the cells extracted from the spinal cords of rats, examined on day 14, that had been treated 1-12 h previously with dexamethasone, than in saline-treated controls. This increased level of apoptosis was observed in the CD5 + and TCR + cell populations. At 1-4 h after dexamethasone treatment there was a reduction in the selective apoptosis of V 8.2 + cells that normally occurs during spontaneous recovery from EAE. Therefore apoptosis of V 8.2 + cells cannot explain the reduction in the numbers of V 8.2 + cells and MBP-reactive cells in the CNS after dexamethasone treatment. By 8-12 h after dexamethasone treatment the selectivity of the apoptotic process was restored. These studies suggest that a reduction in the number of T-lymphocytes in the central nervous system contributes to the beneficial effects of corticosteroids in EAE.