Intranasal administration of recombinant mouse interleukin-12 increases inflammation and demyelination in chronic experimental autoimmune neuritis in Lewis rats.
To examine whether interleukin (IL)-12 modulates ongoing chronic experimental autoimmune neuritis (EAN), we evaluated the effects of recombinant mouse IL-12 (rmIL-12) in Lewis rats with chronic EAN, induced by immunization with P0 peptide (180-199) plus complete Freund's adjuvant. Rats were treated intranasally with either 0.1 or 1 microg/rat/day rmIL-12 for 6 days from the onset of clinical chronic EAN, on days 5-10 postimmunization (p.i.). Only high-dose rmIL-12 exacerbated chronic EAN. This clinical effect was associated with higher numbers of inflammatory cells and more severe demyelination in sciatic nerve sections on days 15 and 80 p.i. compared with low-dose rmIL-12-treated rats and phosphate-buffered saline (PBS)-treated control rats. High-dose rmIL-12 increased significantly the lymph node mononuclear cell proliferation in response to P0 peptide 180-199 and IFN-gamma production in the sciatic nerves. These data indicate that intranasally administered IL-12 acts as a proinflammatory cytokine in chronic EAN. Effective inhibition of IL-12 in vivo could be considered for therapeutic use in chronic inflammatory demyelinating polyradiculoneuropathy.
Pelidou
S H
SH
Division of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Zou
L P
LP
Deretzi
G
G
Nennesmo
I
I
Wei
L
L
Mix
E
E
Van Der Meide
P H
PH
Zhu
J
J
D000281:Administration, Intranasal; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007114:Immunization; D007249:Inflammation / Q000209:etiology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018993:Myelin P0 Protein / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D011129:Polyradiculoneuropathy / Q000209:etiology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology
D000949:Histocompatibility Antigens Class II; D018993:Myelin P0 Protein; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma