Studies on the intrathecal humoral immune response in canine distemper encephalitis

Albumin and IgG were quantitated in paired cerebrospinal fluid (CSF) and serum samples from dogs with demyelinating canine distemper virus (CDV) infection by means of rocket immunoelectrophoresis. The IgG index as indicator for intrathecal immunoglobulin synthesis was normal in animals with non-inflammatory demyelinating lesions and elevated in dogs with inflammatory myelin lesions. Specific antibodies against CDV and myelin were quantitated in CSF and serum from 8 dogs with an elevated IgG index. Eight of these dogs had significant amounts of antimyelin antibody and 4 dogs had neutralizing anti-CDV antibody in the CSF. Whereas the pathogenetic significance of antimyelin antibodies remains uncertain, the intrathecal antiviral immune response provides a plausible explanation for immunopathologic destruction of myelin in distemper.     

The effect of hypothalamic lesions on the immune response in rats

The nervous and immune systems are thought to have important roles in the host defence mechanism. Recent reports have suggested that presence of common antigens between the nervous and immune systems. It would be of interest to know the possibility of mutual relations between both systems. For the purpose of examining the relations, the author investigated peripheral blood lymphocyte blastogenesis, growth curves of inoculated subcutaneous tumor and serum levels of catecholamine and corticosterone, 2 weeks after the bilateral stereotaxic destruction of WKA rat medial hypothalamic nuclei. As a result of hypothalamic destruction, lower stimulation indices to PHA of the lymphocytes in the peripheral blood were obtained in rats with anterior hypothalamic lesions, premamillary lesions and mamillary lesions, and higher stimulation indices in those with dorsomedial hypothalamic lesions. On the other hand, lower stimulation indices to PWM were obtained in rats with dorsomedial hypothalamic lesions and higher ones in those with mamillary lesions. These results may suggest the existence of reciprocal function between the dorsomedial hypothalamic nucleus and mamillary nucleus. To examine the effect of hypothalamic lesions on tumor immunity, subcutaneous tumor inoculation and its growth curves were studied. As the tumor cells of KMT-17 are allogeneic in WKA rats, inoculated subcutaneous tumors grew temporarily and disappeared within 15 days. The peak of the growth curves was raised in rats with anterior hypothalamic lesions. Rats with other hypothalamic lesions and controls showed almost the same growth curves. From the results, it is suggested that the anterior hypothalamic nucleus may have some effect on tumor immunity.(ABSTRACT TRUNCATED AT 250 WORDS)     

The immune response to picornavirus infection and the effect of immune manipulation on acute seizures

Viral infection of the central nervous system can result in encephalitis. About 20% of individuals who develop viral encephalitis go on to develop epilepsy. We have established an experimental model where virus infection of mice with Theiler’s murine encephalomyelitis virus (TMEV) leads to acute seizures, followed by a latent period (no seizures/epileptogenesis phase) and then spontaneous recurrent seizures—epilepsy. Infiltrating macrophages (CD11b⁺CD45^hi) present in the brain at day 3 post-infection are an important source of interleukin-6, which contributes to the development of acute seizures in the TMEV-induced seizure model. Time course analysis of viral infection and inflammatory [CD11b⁺CD45^hiLy-6C^hi] and patrolling [CD11b⁺CD45^hiLy-6C^low] monocyte and T cell infiltration into the brains of TMEV-infected C57BL/6J mice over the entire course of the acute viral infection was performed to elucidate the role of virus and the immune response to virus in seizures and viral clearance. The infiltrating inflammatory macrophages were present early following infection but declined over the course of acute viral infection, supporting a role in seizure development, while the lymphocyte infiltration increased rapidly and plateaued, advocating that they play a role in viral clearance. In addition, we showed for the first time that, while TMEV infection of RAG1^?/? mice did not alter the number of mice experiencing acute seizures, TMEV infection of C57BL/6J mice depleted of macrophages resulted in a significant decrease in the number of mice experiencing seizures, again supporting a role for infiltrating macrophages in the development of acute seizures in the TMEV-induced seizure model.     

The effect of hypothalamic temperature on the immune response in the rat

To clarify the role of febrile temperatures on the immune system, rats were immunized with sheep erythrocytes and their core temperature was then changed by continuously cooling or heating the preoptic area for five days. Core temperatures of up to 2 degrees C above or below normal were associated with a high titre of antibodies against sheep erythrocytes, whereas larger displacements of core temperature, as well as normal temperature, were associated with a low titre. These results are at variance with the idea that the production of antibodies is proportional to body temperature. It is suggested that the immunostimulation elicited by heating and cooling the preoptic area, and by inference that the immunostimulation associated with fever, could be due to factors other than the change in body temperature.     

The relative value of tranquilizing drugs and social and psychological therapies in chronic schizophrenia

Summary Forty-six chronic schizophrenic patients were divided into two groups and treated for six months with tranquilizing drugs in two different settings, a large state hospital and a small treatment center.The rate of improvement was the same at the two hospitals. Marked or moderate improvement was made in one-third of the patients. Another one-fourth was slightly improved and the remainder unimproved.The discharge rate was significantly different at the two hospipitals. Eight patients (33 per cent) were discharged from the small hospital and one patient (5 per cent) was discharged from the large hospital. Discharges were to protected environments, similar in varying degrees to the patient's previous hospital life.The relation of drug therapy to social and psychological therapy in chronic schizophrenia is discussed. Drug treatment appeared to be related to the uniform improvement rate. Intensive social and psychological therapy appeared to increase significantly the discharge rate at the small hospital. The implications of the present study for the management and disposition of chronic schizophrenic patients are listed.Read at the 115th annual meeting of the American Psychiatric Association, Philadelphia, May 1, 1959. The investigation was supported by a research grant, MY-1690 (C2) from the National Institute of Mental Health, Public Health Service. It was sponsored by the Massachusetts Mental Health Center and the department of psychiatry, Harvard Medical School, Boston.     

Studies on the humoral and cell-mediated immune response in a patient with Mollaret's meningitis.

A patient with Mollaret's meningitis with protracted course and a strong immune response within the central nervous system is described. The findings of IgG bands in agarose gel electrophoresis of CSF together with elevated CSF IgG index values are in accordance with intrathecal synthesis of IgG, possibly against an antigen persistent in the CNS. Subgrouping of CSF lymphocytes morphologically (B/T, active T cells) and functionally (stimulation with mitogens) showed that these cells differed from peripheral blood lymphocytes. A defect in the regulatory function of T cells may be responsible for the continuing pathologic process in Mollaret's meningitis.     

Antiepileptic drugs and the immune system

Data on the effects of antiepileptic drugs on the immune system are frequently inconsistent and sometimes conflicting because the effects of drugs cannot be separated from those of seizures, first-generation drugs have been most intensively investigated, the patient's genetic background, the mechanism of action and the pharmacokinetic profile of AEDs and the concurrent use of immunosuppressant drugs may act as confounders. Valproate, carbamazepine, phenytoin, vigabatrin, levetiracetam, and diazepam have been found to modulate the immune system activity by affecting humoral and cellular immunity. AEDs are associated with pharmacokinetic interactions (most frequently occurring with carbamazepine, phenytoin, phenobarbital and valproate). Hepatic metabolism is the primary site of interaction for both AEDs and immunotherapies (ACTH, dexamethasone, hydrocortisone, methylprednisolone, cyclophosphamide, methotrexate, rituximab), which entail induction or inhibition of drug effects. However, the clinical importance of these drug interactions is still far from defined. An important adverse effect of the action of AEDs on the immune system is antiepileptic hypersensitivity syndrome (AHS), a life-threatening, idiosyncratic cutaneous reaction to aromatic AEDs resulting in end organ damage. Phenytoin, carbamazepine, phenobarbital, lamotrigine, oxcarbazepine, felbamate, and zonisamide have been implicated. The pathogenic mechanisms of AHS are incompletely understood.