| First Author | Zhang HL | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 5 | Pages | e38157 |
| PubMed ID | 22666471 | Mgi Jnum | J:187292 |
| Mgi Id | MGI:5436164 | Doi | 10.1371/journal.pone.0038157 |
| Citation | Zhang HL, et al. (2012) Attenuated EAN in TNF-alpha deficient mice is associated with an altered balance of M1/M2 macrophages. PLoS One 7(5):e38157 |
| abstractText | The role of tumor necrosis factor (TNF)-alpha and its receptors in neuroautoimmune and neuroinflammatory diseases has been controversial. On the basis of our previous studies, we hereby aimed to further clarify TNF-alpha's mechanism of action and to explore the potential role of TNF-alpha receptor (TNFR)1 as a therapeutic target in experimental autoimmune neuritis (EAN). EAN was induced by immunization with P0 peptide 180-199 in TNF-alpha knockout (KO) mice and anti-TNFR1 antibodies were used to treat EAN. Particularly, the effects of TNF-alpha deficiency and TNFR1 blockade on macrophage functions were investigated. The onset of EAN in TNF-alpha KO mice was markedly later than that in wild type (WT) mice. From day 14 post immunization, the clinical signs of TNF-alpha KO mice were significantly milder than those of their WT counterparts. Further, we showed that the clinical severity of WT mice treated with anti-TNFR1 antibodies was less severe than that of the control WT mice receiving PBS. Nevertheless, no difference with regard to the clinical signs of EAN or inflammatory infiltration in cauda equina was seen between TNF-alpha KO and WT mice with EAN after blockade of TNFR1. Although TNF-alpha deficiency did not alter the proliferation of lymphocytes in response to either antigenic or mitogenic stimuli, it down-regulated the production of interleukin (IL)-12 and nitric oxide (NO), and enhanced the production of IL-10 in macrophages. Increased ratio of regulatory T cells (Tregs) and reduced production of interferon (IFN)-gamma in cauda equina infiltrating cells, and elevated levels of IgG2b antibodies against P0 peptide 180-199 in sera were found in TNF-alpha KO mice with EAN. In conclusion, TNF-alpha deficiency attenuates EAN via altering the M1/M2 balance of macrophages. |
