The role of the neuroendocrine system in determining genetic susceptibility to experimental allergic encephalomyelitis in the rat.
Experimental allergic encephalomyelitis (EAE) can be induced in some strains of rat but not others, by the injection of guinea-pig myelin basic protein in Freund's complete adjuvant. In the susceptible Lewis strain, spontaneous recovery from paralysis occurs and previous studies have shown that this recovery is dependent on the production, during the course of the disease, of high levels of corticosterone from the adrenal glands. Adrenalectomy completely abrogates the recovery phase and the disease becomes uniformly fatal unless steroid replacement therapy is given, which reproduces the serum levels of hormone that develop in intact animals with EAE. The PVG strain is not susceptible to EAE, but here it is shown that PVG rats that had been adrenalectomized developed severe disease from which they do not recover. As in the adrenalectomized Lewis rat, steroid replacement therapy could prevent the fatal outcome and in this case the disease course resembled that seen in intact Lewis animals. By a number of parameters PVG rats appear to make a more vigorous steroid response to stress than do Lewis. A comparison of the ratio of adrenal weight to body weight between these strains indicated that this ratio is larger in PVG, and serum corticosterone levels, in response to stress, were also found to be higher in this strain. Furthermore, basal levels of corticosterone were much more labile in PVG rats and had a higher mean value than those found in the age- and sex-matched Lewis animals with which they were compared. Genetic analysis using congenic rat strains showed that a high adrenal weight to body weight ratio was not linked to the major histocompatibility complex (MHC). It appears that the resistance to EAE of PVG rats depends on an enhanced stress response that mediates its immunosuppressive effect via the adrenal glands. While this stress response plays an essential part in the recovery of Lewis strain rats from EAE, it is sufficiently potent in PVG rats to virtually completely prevent signs of disease. Resistance to the induction of EAE could not be abrogated by adrenalectomy in all strains of rats studied. In particular, congenic PVG.RT1u rats, with the same background genes as PVG but with RT1u rather than the RT1cMHC genes of PVG, did not develop EAE when the adrenal glands were removed.(ABSTRACT TRUNCATED AT 400 WORDS)
Mason
D
D
Department of Human Anatomy, University of Oxford.
MacPhee
I
I
Antoni
F
F
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D008285:Major Histocompatibility Complex / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D003345:Corticosterone