Immunosuppressive effect of gramicidin S on experimental ocular neuritis and allergic encephalomyelitis.
Investigations were carried out on the immunosuppressive effect of gramicidin S (GrS), a cyclic peptide antibiotic produced by Bacillus brevis, on the onset of experimental ocular neuritis and allergic encephalomyelitis in Lewis rats immunized with rat brain homogenates. The criteria for evaluation of the drug effect were changes in body weight, activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), clinical manifestations such as paralysis of lower extremities and histopathological changes. Clinical symptoms and body weight reduction were effectively prevented by GrS treatment of immunized animals. The activity of the myelin marker enzyme CNPase was markedly decreased in the lumbar spinal cord of encephalitogen-immunized animals on day 16 (ie 16 days after immunization) and the decrease of enzymatic activity was partially prevented by GrS administration. On the other hand, the CNPase activity of the retrobulbar optic nerve of inoculated animals remained essentially the same as that of healthy control animals, although inflammatory changes were prominent in the optic nerve. Histopathological changes observed in the optic nerve and spinal cord of diseased animals were virtually absent in GrS-treated animals. A possible mechanism of the immunosuppressive activity of GrS is discussed.
Matsushima
S
S
Kresge Eye Institute, Wayne State University School of Medicine, Detroit, MI 48201.
Yoshitoshi
T
T
Mahalak
S M
SM
Shichi
H
H
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006096:Gramicidin / Q000494:pharmacology*; D007114:Immunization; D007166:Immunosuppressive Agents; D009900:Optic Nerve / Q000201:enzymology / Q000473:pathology; D009902:Optic Neuritis / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D010727:Phosphoric Diester Hydrolases; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology
D007166:Immunosuppressive Agents; D006096:Gramicidin; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571339:Cnp protein, rat