Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats.
Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ Th1 cells that mainly secrete IFN-gamma and TNF-alpha, important cytokines in the pathophysiology of the disease. Spontaneous remission is, in part, attributed to the down regulation of IFN-gamma and TNF-alpha by TGF-beta. In the current paper, we compared weight, histopathology and immunological parameters during the acute and recovery phases of EAE to establish the best biomarker for clinical remission. Female Lewis rats were immunised with myelin basic protein (MBP) emulsified with complete Freund's adjuvant. Animals were evaluated daily for clinical score and weight prior to euthanisation. All immunised animals developed the expected characteristics of EAE during the acute phase, including significant weight loss and high clinical scores. Disease remission was associated with a significant reduction in clinical scores, although immunised rats did not regain their initial weight values. Brain inflammatory infiltrates were higher during the acute phase. During the remission phase, anti-myelin antibody levels increased, whereas TNF-alpha and IFN-gamma production by lymph node cells cultured with MBP or concanavalin A, respectively, decreased. The most significant difference observed between the acute and recovery phases was in the induction of TNF-alpha levels in MBP-stimulated cultures. Therefore, the in vitro production of this cytokine could be used as a biomarker for EAE remission.
Departamento de Patologia, Universidade Estadual Paulista, Botucatu, SP, Brasil.
Juliana
J
Seger
Sofia Fernanda Gonçalves
SF
Zorzella-Pezavento
Ana Cláudia
AC
Pelizon
Douglas Rodrigues
DR
Martins
Alexandre
A
Domingues
Alexandrina
A
Sartori
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015431:Weight Loss
D015415:Biomarkers; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma