Richard Sowinski

Effects of experimental allergic encephalomyelitis on thymus and adrenal: relation to remission and relapse.

Abstract Experimental allergic encephalomyelitis (EAE) was induced by active immunization with neural tissue and adjuvants and by passive transfer of living lymphoid cells. Severe thymolysis occurred along with severe clinical signs and lesions. Thymolysis was preceded and accompanied by a striking rise in serum corticosterone. Clinical signs then remitted, followed by a decline in serum corticosterone and beginning regeneration of the thymus, but histologic EAE lesions persisted. Adrenalectomy performed early in the remission of EAE was followed promptly by disappearance of serum corticosterone and relapses of clinical signs. Relapses occurred in rats of either sex but not until thymic regeneration had begun. All these data support the theory that nonspecific stress and the state of adrenal hyperactivity in response to neurological disability determine patterns of remission and relapse in EAE by way of immunosuppressive effects on lymphoid tissue.

Plasmacellular lymphadenopathy produced in rats by tin.

Abstract Metallic tin powder induced granulomatous inflammation at the site of inoculation and in draining lymph nodes. In addition, draining nodes were greatly enlarged by proliferation of plasma cells and Russell body cells. Granulomatous response was common to many strains of rats, but only Lewis rats developed striking plasmacellular hyperplasia, and it lasted only about 3 weeks. The spontaneous abatement of the plasma cell response was not due to corrosion of the tin in vivo because tin particles recovered from the tissues 2 weeks after inoculation were still able to induce plasma cells. Treatment of tin with heat, organic solvents, or several oxidizing and reducing reagents did not destroy its potency, but some chemicals diminished its effectiveness by inducing aggregation or stickiness. Other metals, and compounds of tin, did not produce the same reaction. Tin-treated rats had elevated serum IgG but the immunological significance of the plasma cell hyperplasia remains to be elucidated. Although plasmacellular lymphadenopathy was obtained only during a restricted period after inoculation of large doses of tin into a peculiarly susceptible animal, it does have a bearing on the putative role of tin as an essential nutrient and it will be a useful model for study of plasma cell hyperplasia.

Lesions of Amygdala, Pyriform Cortex and other Brain Structures Due to Dipiperidinoethane Intoxication

Single doses of dipiperidinoethane (DPE) produced symmetrical necrosis in pyriform cortex, amygdala and other areas of gray matter in rats, mice and gerbils. The necrosis was detectable in 10 hours and fully developed in 24 hours. Its distribution and severity were not influenced by carotid artery ligation. DPE was not a cumulative poison. There was a high degree of chemical specificity: neurotoxic activity was present in DPE derivatives modified by methylation of the two piperidine rings, but neurotoxicity was absent in derivatives with different ring systems or different connecting chains.

Treatment of experimental allergic encephalomyelitis with myelin basic protein: Which route is best?

When myelin basic protein (BP) has been used for the treatment of multiple sclerosis (MS), it has been injected intramuscularly (IM) or subcutaneously (SC). Experimental allergic encephalomyelitis (EAE) is widely used as a model for MS, and the use of BP for MS is based on its efficacy in EAE. The present work shows that BP is more effective in EAE when administered by intravenous (IV) route than by IM or SC routes. These observations may be pertinent to therapeutic trials in MS.

Periventricular localization of a toxic encephalopathy induced by a mechanism involving choroid plexus

An aliphatic triamine has been reported to cause lesions in rats in the vicinity of the area postrema and the median eminence of the hypothalamus, sites known to lack a blood-brain barrier. The present study revealed that some of the rats developed lesions in the cerebellum as well. The cerebellar lesions were related topographically to the choroid plexus in the underlying fourth ventricle. This periventricular distribution could be due to passage of the triamine from blood to choroid plexus and cerebrospinal fluid and then to parenchyma. In further experiments, the permeability of the plexus was increased by inducing choroid plexitis with cyclophosphamide. Subsequent administration of the triamine induced periventricular cerebellar lesions in higher incidence and at lower dose levels than in normal rats. Thus, the induction of choroid plexitis supported the aforementioned hypothesis and also suggested that it might be a useful model for periventricular localization of other types of lesions or diseases.

Thymolysis induced by EN3638 and other drugs and its relation to immunosuppression

The effect on the thymus of EN3638, an oxime derivative of salicylic acid, was investigated because the drug has immunosuppressive properties. It caused a moderate reduction in thymic weight of normal adult and weanling rats and it retarded the regeneration of the thymus that follows acute corticosteroid-induced involution. These effects of EN3638 were not mediated by the adrenal nor due to the salicylate part of the molecule. At high dose levels, the drug also reduced slightly the weight of spleen and lymph nodes and the rate of body growth. Thymolytic doses of EN3638 were also immunosuppressive for experimental allergic encephalomyelitis (EAE). At doses that caused equivalent degrees of thymolysis. EN3638 was somewhat more potent for suppression of EAE than cyclophophosphamide or hydrocortisone.

Experimental allergic encephalomyelitis: Simple method for producing the localized form

In the past, the lesions of experimental allergic encephalomyelitis (EAE) have been induced to localize around brain tissue damaged by anoxia or direct physical or chemical attack. The procedure for producing the requisite antecedent brain injury has been simplified by use of a single subcutaneous injection of a neurotoxic chemical, thereby eliminating the need for surgery. The EAE lesions are concentrated in a very small area and can be obtained in one day after the passive transfer of a relatively small number of lymph node cells from immunized donors.

Synergistic Suppression of the Hyperacute Form of Experimental Allergic Encephalomyelitis by Tilorone and Cycloleucine

Summary Single doses of antilymphocyte serum, cyclophosphamide, cycloleucine, and tilorone delayed the onset of the hyper-acute form of experimental allergic enceph-alomyelitis. Many combinations of drugs delayed the onset more than the sum of the delays attributed to each agent alone. The efficacy of some combinations depended on the schedule of administration. Cycloleucine and tilorone were proven to have a synergistic relationship.

Macrophages in the omentum: Effects of drugs and pertussis vaccine evaluated by a simple weight assay☆

Abstract Mineral oil was injected into the peritoneal cavity of rats. Two weeks later, the omentum was dissected free of pancreatic tissue in a systematic manner. The weight of the omentum increased two- to threefold due to accumulation of a relatively pure population of oil-laden macrophages. A shorter time period gave a smaller weight increment and a longer interval favored development of fibrous connective tissue. Old animals were unsatisfactory subjects because of the excessive and very variable amounts of fat in the omentum. The weight of the macrophage-laden omentum was used as a simple assay for the delivery and phagocytic functions of the monocyte-macrophage system. Systemic administration of pertussis vaccine or cycloleucine inhibited the accumulation of macrophages in the omentum. Inoculation of oil and weighing of the omentum in the course of routine screening and toxicological testing of drugs could add important information with hardly any extra effort or expense.

Suppression of Experimental Allergic Encephalomyelitis by En3638: Dependence

Oral administration of 2, 3 or 4 doses of 100 or 250 mg/kg of EN3638 during the incubation period of experimental allergic encephalomyelitis delayed the onset and reduced the incidence and severity of clinical signs and histological lesions. Five doses of 50 or 100 mg/kg effected virtually complete and permanent suppression of clinical signs even after cessation of therapy, and five doses of 250 mg/kg eliminated histological lesions as well. Optimum results required coverage of the entire incubation period regardless of dose level. These results were obtained only when carbonyl iron was used as the adjuvant for production of EAE. When complete Freunds adjuvant was used, EN3638 delayed the onset but had little or no influence on late-developing clinical signs and histologic lesions after cessation of therapy. The permanence of suppression when carbonyl iron was used is related to the absence of an oil depot. Carbonyl iron is a superior adjuvant for drug suppression studies.