IFN-beta suppresses experimental autoimmune neuritis in Lewis rats by inhibiting the migration of inflammatory cells into peripheral nervous tissue.
The putative prophylactic and therapeutic effect of interferon-beta (IFN-beta) on autoimmune inflammation of the peripheral nervous system was evaluated in experimental autoimmune neuritis (EAN), a well-known animal model of the human Guillain-Barré syndrome (GBS). We report that treatment of rats with 300,000 U of recombinant rat IFN-beta (rrIFN-beta) given every other day starting at the day of immunization prevented clinical signs of EAN. When treatment was started at the onset of disease development, the cytokine clearly ameliorated EAN. Both B- and T-cell responses towards peripheral myelin were suppressed by the IFN-beta, and immunohistochemical analyses revealed a strong decrease in the numbers of infiltrating CD4(+) T cells, macrophages, and other inflammatory cells as well as a significant reduction in MHC class II antigen expression and monocyte chemotactic protein-1 (MCP-1) production, which induces chemotaxis and chemokinesis of leukocytes from blood. It is concluded that the observed suppression of EAN by rrIFN-beta is associated with a decrease in the migration of inflammatory cells into peripheral nervous tissue.
Zou
L P
LP
Division of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Ma
D H
DH
Wei
L
L
van der Meide
P H
PH
Mix
E
E
Zhu
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002464:Cell Migration Inhibition; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D018932:Chemokine CCL2; D016212:Transforming Growth Factor beta; D016899:Interferon-beta; D007371:Interferon-gamma