Changes of experimental allergic encephalomyelitis by methionine-enkephalin injected into lateral ventricles of the rat brain

Our previous investigations have shown that the opioid peptide methionine-enkephalin (Met-Enk) modulates in vivo a variety of humoral and cell-mediated immune performances. In this study, rats bearing polyethylene cannulae permanently inserted into the lateral ventricles of the brain were used. Experimental allergic encephalomyelitis (EAE) was induced with guinea pig spinal cord in complete Freund's adjuvant injected into the left hind foot pad. The following groups of cannulated rats were tested: nontreated with Met-Enk or saline, intracerebroventricularly (i.c.v.) injected with saline, and i.c.v. treated with low (1ug/kg) dose of Met-Enk and high (1 mg/kg) dose of Met-Enk. Intact noncannulated rats sensitized for EAE served as an additional control. The results showed that i.c.v. treatment with 1 ug/kg of Met-Enk significantly increased the incidence and severity of EAE. In contrast, injections of 1 mg/kg of Met-Enk produced a moderate decline of clinical EAE, but marked diminution of inflammatory lesions in the brain. Interestingly, histopathology of EAE was more pronounced in control rats treated i.c.v. with saline. On the other hand, control cannulated rats noninjected with saline exhibited a striking decrease of neurological and histopathological signs of the disease, thus indicating a suppressive effect of stress (surgical procedure) on EAE. In conclusion, the present study showing the central effect of Met-Enk on EAE when peptide was applied in the cerebral cavity, and earlier studies which revealed the peripheral effect on EAE when Met-Enk was administered intraperitoneally, suggests that Met-Enk exerts its immunomodulatory action both centrally and peripherally.