concanavalin-a and Epilepsy

1. In genetically epilepsy-prone rats (GEPR-9s), which represent a natural genetic model of epilepsy, we observed that the number of peritoneal macrophages was significantly lower with respect to normal rats, and that some functional parameters (i.e. phagocytosis and intracellular killing) of these macrophages were impaired. 2. The count of lymphocyte populations showed a predominance of T-helper over T-cytotoxic/suppressor both in the spleen and lymph nodes. Moreover, an increased T-cell/B-cell ratio was observed in GEPR-9s. Flow cytometry revealed that GEPR-9s spleens possessed a large percentage of T-helper cells in comparison to normal rats. 3. By using concanavalin A-induced proliferation of GEPR-9s cultured lymphocytes, we have shown increased functional activation. 4. We suggest that the alterations in T-cell functions in GEPR-9s could be due to the involvement of the neuroendocrine system in the modulation of immunity, in the shift between Th1 and Th2, and in the activation of stress response.

Topics: Animals; B-Lymphocytes; Cell Membrane; Concanavalin A; Epilepsy; Flow Cytometry; Lymph Nodes; Macrophages; Macrophages, Peritoneal; Organ Size; Phagocytosis; Rats; Rats, Sprague-Dawley; Superoxides; T-Lymphocytes; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer

A number of immune abnormalities have been found in epileptic patients. Several, but not all, of these defects appear to be related to the toxic effects of antiseizure medications. To study the basis of immune abnormalities in epilepsy, various populations and subsets of peripheral blood mononuclear cells (PBMC) from epileptic patients were enumerated and their functions examined. Reduced natural killer cell activity was found in the patients and their siblings. Enumeration of the PBMC showed a lower proportions of Leu 11+ cells in some of the patients which may account for the lower natural killer activity. A reduced ratio of OKT4+/OKT8+ cells was also found in the patients. Responses of patient PBMC to the T-cell mitogens phytohemagglutinin, concanavalin A and the B-cell mitogen pokeweed mitogen were unchanged as were the total number of rosette-forming cells in the patients. The results provide more evidence for a genetic basis for some of the immune abnormalities in epileptic patients.

Topics: Adolescent; Adult; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Child; Child, Preschool; Concanavalin A; Cytotoxicity Tests, Immunologic; Epilepsy; Humans; Killer Cells, Natural; Lymphocyte Activation; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; Rosette Formation; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer

The results of this prospective study fail to confirm previously reported phenytoin suppression of lymphocyte responsiveness to mitogens. Our data show a significantly greater than expected percentage (p less than 0.0001) of patients requiring phenytoin treatment have low lymphocyte responsiveness to mitogens prior to phenytoin therapy. Analysis of changes in each individual's response during phenytoin treatment as compared with their pre-phenytoin responses shows a consistent trend to increased responsiveness to concanavalin A, pokeweed mitogen, and to a suboptimal concentration of phytohemagglutinin. This trend was most pronounced for patients whose serum IgA concentration was decreased while taking phenytoin, whereas there was no such trend for individuals whose serum IgA levels were not decreased. This phenomenon was not related to neurological disease classification. Phenytoin added directly to lymphocyte cultures depressed lymphocyte responses to all mitogens in a small (less than 20%) but significant degree, confirming similar in vitro studies by other investigators. Because of limited serum proteins for phenytoin binding in culture medium, these in vitro studies have little application to possible phenytoin effects on lymphocytes of patients taking it to prevent seizures. Thus, the suggestion that phenytoin causes depressed lymphocyte responses to mitogens in epileptic patients appears unwarranted.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Concanavalin A; Epilepsy; Female; Humans; Immunoglobulin A; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Phenytoin; Phytohemagglutinins; Pokeweed Mitogens; Prospective Studies