Enkephalins and autoimmunity: differential effect of methionine-enkephalin on experimental allergic encephalomyelitis in Wistar and Lewis rats.

To evaluate the immunomodulating activity of methionine-enkephalin (Met-Enk) and leucine-enkephalin (Leu-Enk) in the development of experimental allergic encephalomyelitis (EAE), two strains of rats, one highly susceptible to EAE (Lewis rats) and the other relatively resistant to the disease (Wistar rats) were used. The animals were given daily injections of either a high dose (5 mg/kg b.w.) or a low dose (0.2 mg/kg b.w.) of these opioid peptides, after receiving guinea pig spinal cord in combination with immunological adjuvants. A major conclusion from this study is that Met-Enk is a potent immunomodulator/regulator of the autoimmune disease, whereas Leu-Enk does not affect EAE. The high dose of 5 mg/kg b.w. of Met-Enk completely or significantly inhibited neurological signs and markedly diminished occurrence and intensity of histological lesions in the brain, and cervical, thoracic, and lumbar spinal cord. The loss of body weight, which accompanies EAE, was also prevented by a high dose of Met-Enk. In contrast, the low dose of 0.2 mg/kg b.w. of Met-Enk potentiated neurological and histopathological features of the disease. Nonimmunized rats injected with enkephalins for a period of 17 consecutive days showed neither neurological nor histological signs of EAE, nor signs of intoxication due to the application of enkephalins. Thus, these data establish a link between methionine-enkephalin and EAE, and suggest that this opioid pentapeptide might be important in the pathogenesis and prevention of the inflammatory autoimmune disease.