Effects of human recombinant-interferon β in experimental autoimmune encephalomyelitis in guinea pigs.
BACKGROUND
Although clinical data for beneficial effects of Betaferon, human recombinant-interferon (r-IFN) β-1b, are accumulating, what is less evident is how and why it works.


OBJECTIVE
The present study was carried out to examine whether Betaferon suppresses progression of experimental autoimmune encephalomyelitis (EAE).


METHODS
The EAE model was employed in guinea pigs in vivo, and mononuclear cell proliferation and 2',5'-oligoadenylate synthetase activity were assessed in vitro.


RESULTS
Betaferon was more reactive in two assays of guinea pigs, mitogen-induced proliferation of peripheral blood mononuclear cells and 2',5'-oligoadenylate synthetase activity of blood, than in rats and rabbits. Guinea pigs were immunized actively by antigen, porcine myelin basic protein. The neurological deficits were assessed by clinical signs scored daily. Guinea pig Betaferon, replaced with guinea pig albumin (GPA), at 1.2 and 12.0 MIU/kg/day or vehicle was administered subcutaneously daily for 20 days in the immunized guinea pigs. GPA-Betaferon suppressed the manifestation of ataxia or more progression of chronic neurological deficits significantly at 1.2 MIU/kg (p <0.05). Two out of 10 animals manifested no clinical signs in the GPA-Betaferon-treated group with the higher dose, while all animals were worsened with typical clinical signs of EAE in the vehicle group where mononuclear cell infiltrates around blood vessels were seen in the spinal cord of vehicle-treated animals.


CONCLUSIONS
Human r-IFN β-1b attenuates progression of neurological deficits in the EAE model of guinea pigs with evidence for higher susceptibility of animal cells/tissues to the human cytokine, in contrast with rodents and rabbits.
Aritake
Kosuke
K
Preclinical Department of Research and Development, Nihon Schering, Osaka, Japan.
Koh
Chang-Sung
CS
Inoue
Atsushi
A
Yabuuchi
Fumie
F
Kitagaki
Kunihiko
K
Ikoma
Yukihiro
Y
Hayashi
Shigehiro
S
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000473:pathology; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013045:Species Specificity
D000276:Adjuvants, Immunologic; D004676:Myelin Basic Protein; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase