Cytokine-producing cells in experimental autoimmune encephalomyelitis and multiple sclerosis

Abstract

In both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis, the regulation of the cytokine spectrum and production is likely to have a decisive influence on disease outcome. Studies of cytokines, however, are hampered by the autocrine or paracrine nature of cytokines. Studies of cellular production by messenger RNA detection or cellular secretion are therefore necessary. Collective data suggest that certain cytokines associated with the TH1 phenotype or lymphocytes, such as tumor necrosis factor alpha, lymphotoxin, interleukin-12, and interferon gamma, may promote disease, while cytokines produced by the TH2 subset, such as interleukin-10, may limit disease. In addition, transforming growth factor beta is a putative disease downregulator. Increased knowledge in this field will likely lead to improved therapy for MS patients.

Decreased in vitro production of interferon-gamma and interleukin-2 in whole blood of patients with schizophrenia during treatment

“…55,56 In multiple sclerosis, IFN-␥ seems to promote the disease process. 57 An elevated production was found which preceded the manifestation of clinical symptoms, 58 although this was not seen in acute episodes or remissions. 48 Despite the fact that the complex pathophysiological functions of TH1-cytokines in autoimmune disorders are not yet fully understood and that the above mentioned inconsistencies of data remain to be clarified, mounting evidence suggests a major role for these (and other) cytokines, not only as indicators of T cell activity but also as direct inflammatory agents.…”

RGMA and IL21R show association with experimental inflammation and multiple sclerosis

“…17 Experimental autoimmune encephalomyelitis (EAE), a model for MS, has defined pathogenic mechanisms underlying neuroinflammation, and has allowed development of treatments for MS. 18 Experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycopreotein (MOG) in rats closely mimics clinical and pathological features of human MS. 19 Furthermore, the cytokine orchestration in MS and EAE correlate well. [20][21][22] Similarly, various animal models for RA have been used, with pristane-induced arthritis (PIA) being the model of choice for studies on erosive RA and acute-phase responses in arthritis. 23 It best fulfills the criteria for diagnosis of RA 24 and is characterized by pronounced bone and cartilage erosions, presence of serum rheumatoid factors and T-cell infiltrations in joints.…”

Cytokine gene therapy of autoimmune demyelination revisited using herpes simplex virus type-1-derived vectors

“…13 Finally, evidence in humans is paralleled by those obtained in EAE: (1) myelin-specific Th1 cell lines and clones transfer EAE to syngenic recipients; 3,14 (2) mRNA and protein levels of Th1 cytokines increase before the onset of clinical EAE signs and then parallel EAE progression; 14,15 and (3) MBP-specific T cells from non-human primates producing Th1 cytokines are able to induce EAE upon transfer into irradiated autologous recipients.…”