IL-10 fails to abrogate experimental autoimmune encephalomyelitis.
Mice adoptively-sensitized to develop chronic relapsing experimental autoimmune encephalomyelitis (EAE), a model for the human demyelinating condition, multiple sclerosis (MS), were given injections of recombinant human IL-10 at various timepoints post-sensitization in an attempt to abrogate disease development. IL-10 is a Th2 immunomodulatory cytokine with known down-regulatory effects upon Th1 responses and macrophages. Contrary to a previous report on EAE and the predicted outcome, after repeated experiments, IL-10 was found to elicit a worsening or no effect upon EAE in the mouse. Animals were studied clinically, histopathologically and immunocytochemically. On no occasion was disease ameliorated by IL-10. Pretreatment with IL-10 of lymph node cells used to transfer EAE had no effect upon disease outcome, indicating that the cells were already committed effectors. Administration of anti-IL-10 monoclonal antibody before onset of signs had no effect when given early post-sensitization and caused marked worsening when given immediately before onset of signs. In the context of this autoimmune demyelinating model, these results suggest that IL-10 alone is insufficient to reverse the effector response and indeed may serve to enhance the cascade of events in EAE.
Cannella
B
B
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Gao
Y L
YL
Brosnan
C
C
Raine
C S
CS
D019264:Adoptive Transfer; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000627:therapeutic use*; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
D011994:Recombinant Proteins; D016753:Interleukin-10