Search

T cell vaccination, which protects rodents against experimental autoimmune encephalomyelitis (EAE), has been shown to induce anti-idiotypic response in the T cell compartment. CD5 B cells (B1 cells) are the main source of natural autoantibodies, and are often characterized by high idiotypic connectivity. In this study we examined the possibility that idiotypic connectivity in the B cell compartment may also play a role in the regulation of EAE. We inoculated CSJLF1 mice (H-2d,s) with a CD5 B cell line, the BCL1 lymphoma cells (H-2d), and subsequently induced EAE. The injection of as few as 1,000 BCL1 lymphoma cells significantly blocked the development of EAE. Injection of CD5-negative myeloma cells (SP2) had no effect on the pathogenesis of the disease. Unlike control animals, lymphocytes from BCL1 lymphoma-injected mice significantly proliferate in response to interleukin-5, a growth factor to CD5 B cells. The proliferative response of lymphocytes from BCL1 inoculated mice to mitogenic stimulation was rather unchanged, indicating that no general immunosuppression has been induced by inoculating BCLJ lymphoma. These experiments suggest that CD5 B cells may be involved in the regulation of EAE.

Glucocorticoids are frequently employed as immunosuppressive agents. Following clinical reports of occurrence and exacerbation of neurological immune-mediated conditions in patients receiving steroids, we studied the course of experimental allergic encephalomyelitis (EAE) in rats receiving methylprednisolone prior to and during disease induction and after the appearance of clinical signs. High methylprednisolone dose given prior to EAE induction significantly increased disease duration and the number of days at maximal disability. When the drug was given prior to and during the induction phase, both moderate and high doses exacerbated the EAE course. In contrast, treatment with methylprednisolone after the onset of clinical disease had a markedly beneficial effect. Thus, time of initiation, dosage and duration of treatment may differentially affect the course of EAE. Moreover, the natural course of a neurological immune-mediated condition may be worsened when it is triggered while the patient is under steroid treatment.

The influence of experimental autoimmune encephalomyelitis (EAE) on the course and outcome of pregnancy, and the effect of pregnancy on EAE development, was investigated in rabbits and rats. Animals were immunized with encephalitogenic antigen in complete Freund's adjuvant (CFA) either before or during pregnancy. Abortion or fetal resorption was observed in most of the rabbits immunized before or during pregnancy, but not in pregnant rabbits injected with CFA or saline alone. Fetal loss was higher in those rabbits that developed clinical EAE. In rats, fetal loss occurred only when immunization was carried out during the first half of pregnancy. The appearance of EAE in pregnant rabbits, but not in rats, was delayed until after abortion or termination of pregnancy. The incidence of EAE in rabbits was lower, with milder severity and longer duration. Serum antibody levels to myelin basic protein, the autoantigen of EAE, was lower in pregnant rabbits, but not in rats, as compared to non pregnant animals. These results indicate that in species where pregnancy has a suppressive influence on the development of experimental autoimmune demyelinating disease, immunization with the neuroantigen induces a high rate of fetal loss.

A group of myasthenia gravis (MG) patients was studied in order to demonstrate the differential ability of acetylcholine receptor (AChR) antibodies to bind to AChRs from different sources. Four different AChR sources were used: human muscle, denervated rat muscle, normal rat muscle and the electric organ of the electric ray, Torpedo californica. We demonstrated that AchR antibodies from MG patients tested reacted best with receptors from human muscle, and least with the electric ray receptor. The patients were classified into three categories, each representing an antibody level pattern. THe most common pattern was that in which the antibody level for human AchR is highest, followed by decreasing values for AchRs of denervated rat muscle, normal rat muscle, and that of the electric organ of the electric ray. No correlation was found between the patient-specific antibody pattern and a clinical description of the MG patient.

We studied the ability of alpha-fetoprotein (AFP) to suppress experimental allergic encephalomyelitis (EAE) in rabbits. Animals were treated with daily injections of 50 micrograms of AFP following the onset of neurological signs. Clinical status, anti-myelin basic protein (MBP) antibody titers, and histopathological changes in the CNS were determined. Treatment with AFP significantly improved the clinical scores of the affected rabbits and inhibited the binding of anti-MBP antibodies to MBP in vitro. However, there was no significant difference in the titers of anti-MBP antibody, and no amelioration of histopathological changes between treated and control animals. We conclude that AFP is effective in improving the clinical status of animals with EAE, even after the appearance of clinical signs.

The pharmacokinetics and bioavailability of valproic acid (VPA) were compared in six healthy volunteers after oral administration of the drug as follows: 1 g in standard tablet form, 1 g in enteric-coated tablet form, and 0.8 g in gelatin-capsule form. Following the administration of standard tablets, VPA concentrations reached a peak mean +/- SD of 105.4 +/- 9.0 micrograms/ml at 1 h and declined monoexponentially, with a terminal half-life of 14.9 +/- 2.4 h. Following the administration of the capsule, the serum concentration reached a peak of 82.1 +/- 14.8 micrograms/ml at 4 h. Following the administration of an enteric-coated tablet, there was an average time lag of 2 h with a delayed peak serum concentration of 93.5 +/- 13.1 micrograms/ml at 6 h. An identical terminal half-life of VPA was obtained for the three oral formulations. The bioavailability of the three VPA formulations was not significantly different, and it may be concluded that these formulations are bioequivalent.