Myelin
basic protein (MBP) induced experimental autoimmune
encephalomyelitis (EAE)
Agnello D, Bigini P, Villa P, Mennini T, Cerami A, Brines M, Ghezzi P.Erythropoietin
exerts an anti-inflammatory effect on the CNS in a model of experimental
autoimmune encephalomyelitis.Brain Res. 2002 Oct
11;952(1):128.PMID: 12363412 [PubMed - in process]
In recent work we reported that systemically administered
erythropoietin (EPO) crosses the blood-brain barrier and has protective effects
in animal models of cerebral ischemia, brain trauma and in a rat model of
experimental autoimmune encephalomyelitis (EAE). Here we characterize the effect
of systemic EPO on the inflammatory component of actively induced, acute EAE in
Lewis rats. Administration of EPO at doses of 500-5000 U/kg bw i.p., daily from
day 3 after immunization with myelin basic protein (MBP), delayed the onset of
EAE and decreased its clinical score at peak time (days 12-13).
Immunohistochemical analysis of the spinal cord using anti-glial fibrillary
acidic protein (GFAP) and anti-CD11b antibodies showed that EPO markedly
diminished inflammation and glial activation/proliferation. EAE induced
significant levels of TNF and IL-6 in the spinal cord, where IL-6 was maximum at
the onset of the disease (day 10) and TNF at its peak (day 12). EPO delayed the
increase of TNF levels, without altering their peak levels, and markedly reduced
those of IL-6 suggesting that the decreased inflammation and clinical score may
be in part upon attenuation of IL-6. On the other hand, EPO was without effect
in a model of adjuvant-induced arthritis in Lewis rats, suggesting a specificity
towards autoimmune demyelinating diseases. These data suggest that EPO might act
as a protective cytokine in inflammatory pathologies of the CNS.
The Wistar Kyoto (RT1(l)) rat is resistant to myelin basic
protein-induced experimental autoimmune encephalomyelitis: comparison with the
susceptible Lewis (RT1(l)) strain with regard to the MBP-directed CD4+ T cell
repertoire and its regulation.
J Neuroimmunol. 2002 May;126(1-2):25-36.
PMID: 12020954 [PubMed - indexed for MEDLINE]
The effects of pregnancy on myelin basic protein-induced
experimental autoimmune encephalomyelitis in Lewis rats: suppression of clinical
disease, modulation of cytokine expression in the spinal cord inflammatory
infiltrate and suppression of lymphocyte proliferation by pregnancy sera.
Am J Reprod Immunol. 2001 Dec;46(6):405-12.
PMID: 11775010 [PubMed - indexed for MEDLINE]