Eugene J. Wenk

Suppression of experimental allergic encephalomyelitis by stress.

Summary Stress, in the form of restraint repeated throughout the experiment or during its first half, suppressed development of clinical and histologic signs of experimental allergic encephalomyelitis (EAE) in rats after intradermal challenge with encephalitogenic emulsion. Clinical signs, but not histologic lesions, were suppressed by restraint when the highly effective foot pad route of challenge was employed. Intraperitoneal injections of adjuvant also suppressed EAE in rats simultaneously challenged with encephalitogenic emulsion in the skin. It is suggested that suppression of EAE by intraperitoneal adjuvant was due to the stressful effects of the consequent sterile granulomatous peritonitis. Thus, the occurrence of granulomatous peritonitis may explain the failure to produce EAE when rats are challenged by intraperitoneal route with encephalitogenic emulsions that contain adjuvant.

Passive Transfer Of Allergic Encephalomyelitis Between Inbred Rat Strains: Correlation With Transplantation Antigens

Experimental allergic encephalomyelitis (EAE) was elicited in donor Lewis rats by immunization with heterologous spinal cord antigen and adjuvants. Suspensions of cells from their draining lymph nodes transferred the disease passively to normal isohistogenic Lewis recipients and to genetically tolerant (Lewis X BN) or (Lewis X Buffalo)F1 hybrids, in all of which Lewis cells should enjoy extended survival. However, in accordance with the rules of transplantation genetics responsible for homograft rejection, transfers of such Lewis cells to normal BN, Buffalo, ACI and Wistar/Furth recipients were not effective, nor were transfers of cells from immunized hybrid donors to normal Lewis recipients. Donor cells would not be expected to survive in these situations. On the other hand, transfers of immmunized Lewis cells to Fischer 344 recipients were successful, especially after adrenalectomy of recipients or focal impairment of their blood-brain barrier by cyanide treatment. This inter-strain transfer of EAE was attributed to genetic identity of these two strains at a major histocompatibility locus, and was obtained despite differences at minor histocompatibility loci. There was no evidence of a significant Y-linked histocompatibility factor in this system.

Allergic Neuritis Induced in Rats Without the Use of Mycobacteria.

Summary Experimental allergic neuritis was produced in rats by a single injection of peripheral nerve antigen with “incomplete”adjuvant. Thus, mycobacteria were not essential components of the adjuvant. The incidence of neuritis depended on the strain of rats and the source of antigen. There was some overlap (“cross reactions”in both directions) in the involvement of rat peripheral and central nervous systems following challenge with peripheral and central antigens.

Enhancement of experimental allergic encephalomyelitis by adrenalectomy.

Summary Adrenalectomy or adrenal enucleation increased the incidence and severity of experimental allergic encephalomyelitis in rats. This effect was reversed by cortisone. These data are related to the effects of adrenalectomy and steroids on inflammatory lesions in inoculation sites and draining lymph nodes, but other mechanisms are not excluded.

Encephalitogenic Potencies of Nervous System Tissues.

Summary Tests of spinal cord, brain, white matter, gray matter, glioma, pineal and peripheral nerve tissue homogenates emulsified in Freunds complete adjuvant indicate that, in the rat, encephalitogenicity is proportional to content of CNS myelin. The distribution of the organ-specific encephalitogenic antigen in CNS myelin extends further down the evolutionary tree than has been recognized heretofore, as turtle or even frog spinal cord can produce EAE in rats.

Fine structure of contrasting choroid plexus lesions caused by tertiary amines or cyclophosphamide.

Hydropic alterations of the fine structure of the choroid plexus epithelium following administration of three different tertiary amines to rats were compared with alterations produced by cyclophosphamide and with normal choroid plexus. Single doses of 2, 7-bis(2-(diethylamino)-ethoxy)- 4− methyl-1,8-naphtyridine HCI or 2,6,-di-(omega-dimethyl aminoethoxy)-pyridine produced dramatic accumulations of membrane-limited vacuoles. Multiple doses of 2,7-bis-(diethylaminoethoxy) fluoren-9-one HC1 (tilorone) produced accumulations of dense cytoplasmic bodies in choroid epithelia cells in addition to the hydropic vacuoles. Differential responses to these agents suggested functional specialization or temporal variation in function among adjacent choroidal cells. Despite the occurrence of pronounced plasma exudation in the plexitis following cyclophosphamide treatment, there was no hydropic vacuolization.

Effect of induced localization on incidence and distribution of experimental allergic encephalomyelitis.

IN THE PRESENT STATE of knowledge, it seems possible that the mechanism involved in remissions in multiple sclerosis is related to that which operates to produce remissions in experimental allergic encephalomyelitis (EAE) . Prigal1 has suggested that remissions in EAE (and perhaps in multiple sclerosis) are due to combination of brain antigen with antibrain antibody. The work reported here is an attempt to determine whether damaged brain tissue can absorb enough of the noxious agent (antibody?) of EAE to influence the course of the experimental disease. Clark and Bogdanove2 showed that electrolytic lesions and other forms of brain damage induced localization of EAE in the adjacent tissue. Levine3 showed localization of EAE in and around cyanide lesions. Both the electrolytic and cyanide lesions were permeable to trypan blue, suggesting that increased penetration of a noxious agent may have been responsible for localization. EAE in the normal rat affects the spinal cord more than the forebrain,3.4 but some rats with induced forebrain localization around cyanide lesions of the corpus callosum, corpus striatum, and other areas had little or no EAE in their cords.Ci This observation raised the possibility that the cord had been protected because the presumed noxious agent of EAE had been diverted to and absorbed by the f~rebra in ,~ analogous to the diversion of noxious agent by parenteral injection of brain tissue (“substitute brain”) .5 Such a mechanism, if confirmed, might provide evidence for the theory that spontaneous remissions in EAE are due to absorption of noxious agent in the EAE lesions. The present experiments were designed to elucidate the extent

Allergic Encephalomyelitis: Rapid Induction without the Aid of Adjuvants

Rapid production of allergic encephalomyelitis has heretofore required injection of nervous tissue emulsified in immunologic adjuvants. Adjuvants are not required if large doses of a potent nervous-tissue anttigen and a highly susceptible strain of rats are used. Susceptibility was increased in animals inoculated beforehand with pertussis vaccine.

Studies on mechanism of ascites produced by pertussis vaccine.

Summary Rats sensitized and challenged intraperitoneally with pertussis vaccine developed severe ascites. However, pertussis vaccine that had been heated for 1 hour at 100°C neither sensitized rats for subsequent challenge nor elicited ascites in adequately sensitized rats. Unheated pertussis vaccine caused lesions in omentum, lymph nodes and spleen, and excessive gain in weight. These were not observed in animals injected with heated vaccine. Sensitization for production of ascites by pertussis vaccine was transferred passively to normal rats by intraperitoneal injection of lymph node cells but not serum obtained from sensitized rats. The results suggest that ascites elicited by pertussis vaccine resembles the delayed type of hypersensitivity and is not related to endotoxin.

Lymphatic dissemination of encephalitogenic emulsion and its relation to prevention of allergic encephalomyelitis by lymphadenectomy.

Summary Encephalitogenic emulsion was widely disseminated in superficial and retroperitoneal lymph nodes following inoculation into the foot pad of rats. Therefore, it was not possible to prevent experimental allergic encephalomyelitis (EAE) by removing only popliteal and inguinal nodes. In contrast, dissemination was more restricted following flank inoculation so that EAE was prevented by homolateral or bilateral excision of axillary, inguinal and elbow nodes, either on day of challenge or 7 days later. Interruption of lymphatic vessels during surgery near lymph nodes (as in “sham” operations), the stressful effects of surgery, and the redistribution of emulsion following elimination of customary drainage pathways were also found to affect experiments designed to influence EAE by lymphadenectomy.