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The susceptibility of homozygous BSVS mice to acute disseminated encephalomyelitis (ADE) has been found to be nutritionally dependent. On a laboratory stock regimen of commercial fox chow pellets, whole wheat bread, and milk this genotype is 100 per cent susceptible to the disease. On a "synthetic" diet, containing a minimal list of vitamins adequate for growth and maintenance, susceptibility was found to be reduced to 15 per cent. Supplementation of the "synthetic" diet with biotin, folic acid, and vitamin B12 restored susceptibility to a frequency of 70 per cent. Increasing the supplements tenfold had no further effect in restoring susceptibility frequencies to the 100 per cent level. In the restoration of susceptibility, folic acid and vitamin B12 were equally effective as single supplements and equivalent to the triple vitamin supplement. The effect of single biotin supplementation was less. An outbreak of fatal pasteurellosis among BSVS mice latently infected with Pasteurella and used in an ADE susceptibility test has been described. The fatal pasteurellosis has been ascribed to a constellation of determinants including (a) diet, (b) sex, (c) inoculation events, and (d) latent infection with Pasteurella. With males the susceptible sex it was possible to avert the fatal pasteurellosis and continue the nutritional experiments by using females exclusively.

ConclusionBy manipulations here described it was possible to induce acute disseminated encephalomyelitis in mice in a shorter time than heretofore, with fewer inoculations and with uniform response. The improved method consists of the intraperitoneal injection of H. pertussis vaccine followed by 2 spaced intracutaneous injections of proteolipide A + B prepared in a Freund-type adjuvant.

The production of EAE in the fully susceptible BSVS mouse genotype has been found to be dependent on the ratio of proteolipid antigen and adjuvant mycobacterial concentration as used in the emulsion, of the Freund type. Disturbance of this ratio, by manipulation of either component, by diminution or increase, results in a decrease in the frequency by which EAE is produced. Simultaneous reduction of antigen and mycobacteria, so that the ratio remains unchanged, retains the full EAE-producing power of the emulsion. The limit of this has not been ascertained. Emulsifying agents have been found to restrict further the permissible limits of the antigen-mycobacterial ratio for full EAE production. Such effects of the emulsifier have been found to vary with the qualitative nature of the emulsifier. Aquaphor has been found to be less restrictive than falba. These phenomena, systematically analyzed here for the mouse, may have an application for other antigen-adjuvant systems and for other hosts.

ConclusionsAn examination of 4 lines of inbred mice for susceptibility to experimental acute disseminated encephalomyelitis revealed a resistant line, BRVR, and a susceptible line, BSVS. The simplest explanation of the data here presented is that the 2 appear to differ by two resistance-conferring genetic factors either of which is adequate to bring about resistance.

Susceptible (BSVS) and resistant (BRVR) mice were experimentally infected with Salmonella typhimurium. The double strain inoculation technique was used in which both avirulent and virulent representatives of S. typhimurium were admitted into the hosts. The BSVS mice succumbed without exception while the BRVR mice survived to 52 per cent. No deaths occurred during the experimental period in non-infected control mice. Parallel to the survivorship test, and concurrent with it, the activity of the reticulo-endothelial system (RES) was measured at frequent intervals in identically infected BSVS and BRVR mice and in their non-infected controls. For this measurement the carbon clearance method was used. No pre-infection difference of activity of the RES could be discerned in susceptible BSVS mice vs. resistant BRVR. Following infection, increases in the RES activity were detected in about the same magnitude in both mouse stocks. However, a difference was found in the time of onset. The susceptible animals showed an early and short increase in the activity of the RES, followed by a drop to control levels at the time of death. The resistant group exhibited a considerably delayed, but significant increase in RES activity, which returned to control levels approximately 4 weeks after infection. The absolute white blood count did not undergo significant change in either of the two infected groups, but the susceptible animals showed a relative increase of their neutrophils at the expense of their lymphocytes. Extensive anatomical changes were observed in both mouse strains, mainly confined to liver and spleen. These consisted of stasis, swelling of Kupffer cells, necrotic foci, histiocytic-monocytic nodules, widespread thrombosis of branches of the portal and splenic veins, and extensive areas of necrosis. These changes appeared earlier in susceptible than in resistant animals. The implications of these findings are discussed.

THE pathogenesis of experimental allergic encephalomyelitis (EAE) is not definitely known and yet it is frequently used as an experimental model for the study of autoimmune disease of the central nervous system. Waksman contends that the principal event giving rise to EAE after injection of the antigen is the passage of immunologically competent cells or histiocytes through small venules into the nervous system1. These cells originate in the blood stream and are held responsible for the destruction of elements containing antigen in the central nervous system by an undefined mechanism. It has been found that EAE can be suppressed, either by generalized physical or chemical cytotoxic agents, or by destruction of the regional lymph nodes draining the inoculation site2–9. This communication reports the suppressive effect of localized irradiation of the brain in mice during the induction of EAE, and compares the effect with that of total body irradiation.