CNS immune responses following experimental stroke.
OBJECTIVE
Animals subjected to an inflammatory insult with lipopolysaccharide (LPS) at the time of stroke are predisposed to develop a detrimental autoimmune response to myelin basic protein (MBP). In this study, we sought to determine whether other inflammatory stimuli could similarly invoke central nervous system (CNS) autoimmunity and whether these detrimental autoimmune responses occurred to antigens other than MBP.


METHODS
Male Lewis rats underwent 3 h middle cerebral artery occlusion (MCAO) and received intraperitoneal injections of LPS, staphylococcal enterotoxin B (SEB), lipoteichoic acid (LTA) or saline at the time of reperfusion. Behavioral tests were performed at set time intervals after MCAO and animals were sacrificed at 1 month to analyze the immune response to MBP, neuron specific enolase (NSE) and proteolipid protein (PLP).


RESULTS
Lymphocytes from SEB treated animals were highly reactive to all tested CNS antigens, but treatment with LPS was most likely to lead to a TH: 1(+) response. A TH: 1(+) response to MBP, NSE or PLP in spleen was associated with worse outcome, although the response to NSE was most predictive of poor outcome. Animals with a cell mediated autoimmune response to either MBP or NSE in spleen had a concomitant humoral response to these antigens.


CONCLUSIONS
These data show that LPS, but not other inflammatory stimuli, increase the likelihood of developing a detrimental autoimmune response to an array of brain antigens.
Zierath
Dannielle
D
Department of Neurology, University of Washington School of Medicine, Harborview Medical Center, Box 359775 HMC, 325 9th Ave, Seattle, WA 98104-2499, USA.
Thullbery
Matthew
M
Hadwin
Jessica
J
Gee
J Michael
JM
Savos
Anna
A
Kalil
Angela
A
Becker
Kyra J
KJ
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000276:immunology / Q000503:physiopathology; D054428:Chemokine CX3CL1 / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007372:Interferons / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D009474:Neurons / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology / Q000503:physiopathology; D020521:Stroke / Q000276:immunology* / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D001323:Autoantibodies; D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D007372:Interferons