Anti-cytokine autoantibodies in experimental autoimmune neuritis in Lewis rats.
Experimental autoimmune neuritis (EAN) is a CD4+ T-cell-mediated, inflammatory demyelinating disease of the peripheral nervous system (PNS) that serves as a model for Guillain-Barre syndrome (GBS) in humans. Cytokine production has been suggested to act a pathogenic role for EAN. To study the potential role of cytokines in context with cytokine autoantibodies (Aabs) in EAN, we used in situ hybridization to detect mRNA expression of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-4, IL-10, and transforming growth factor (TGF)-beta in lymph node mononuclear cell (MNC) and in sciatic nerve sections, as well as ELISA for detection of their autoantibodies in sera and cerebrospinal fluid (CSF) over the course of EAN. Increased mRNA expression for IFN-gamma and TNF-alpha was registered correlating with the peak of clinical signs of EAN, and high levels of mRNA expression for IL-4, IL-10, and TGF-beta were associated with EAN recovery. The levels of cytokine mRNAs were generally inversely correlated to their autoantibodies in serum and CSF, whereby the CSF levels were equal to or lower than the serum levels. Autoantibodies to IFN-gamma dose-dependently inhibited IFN-gamma-induced MHC expression by peritoneal macrophages proving a neutralizing biological effect of these autoantibodies. Our data demonstrate the existence of the anti-cytokine autoantibodies in the sera and CSF of rats with EAN; however, the role of anti-cytokine autoantibodies in the disease process of EAN remains to be resolved.
Zhu
Wei
W
Department of Otorhinolaryngology, the First Hospital, JiLin University, Changchun, China.
Mix
Eilhard
E
Nennesmo
Inger
I
Adem
Abdu
A
Zhu
Jie
J
D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017403:In Situ Hybridization; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000276:immunology
D001323:Autoantibodies; D016207:Cytokines; D012333:RNA, Messenger