TY - JOUR
T1 - IL-10 suppresses experimental autoimmune neuritis and down-regulates T(H)1-type immune responses
AU - Bai, Xue Feng
AU - Zhu, Jie
AU - Zhang, Guang Xian
AU - Kaponides, Georgios
AU - Höjeberg, Bo
AU - Van Der Meide, Peter H.
AU - Link, Hans
PY - 1997/5
Y1 - 1997/5
N2 - Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated monophasic inflammatory disorder of the peripheral nervous system (PNS). Cellular mechanisms, including macrophage and T cell infiltration, and cytokines like IFN-γ and TNF-α are intimately involved in the pathogenesis of EAN. Interleukin 10 (IL-10) is a T(H)2-type cytokine that suppresses monocyte and T(H)1 cell functions. We examined the effect of recombinant human IL-10 (rHuIL-10) in EAN. When administered from the start of immunization with bovine peripheral myelin emulsified in Freund's complete adjuvant, IL-10 effectively suppressed and shortened clinical EAN. Even when given after Day 12 post immunization (pi) after clinical EAN had been established, IL-10 also effectively suppressed the severity of EAN. Pheripheral nerve myelin antigen-reactive IFN-γ-secreting T(H)1-like cells were decreased in lymph nodes from IL-10-treated compared to control EAN rats. PNS autoantigen-induced T cell proliferation and B cell responses were not affected. P2 protein-reactive IFN-γ, TNF-α, IL-1β, and IL-6 mRNA-expressing lymph node cells were also downregulated in IL-10-treated compared to control EAN rats at Day 14 and 26 pi, while P2-reactive IL-4 mRNA-expressing cells were upregulated throughout treatment. Also, in IL-10-treated EAN rats, upregulated anti-P2 IgG1 and downregulated IgG2a were observed. Our results clearly show that rHuIL-10 can suppress clinical EAN, and this suppression is associated with downregulation of T(H)1 responses and macrophage function and upregulated T(H)2 responses.
AB - Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated monophasic inflammatory disorder of the peripheral nervous system (PNS). Cellular mechanisms, including macrophage and T cell infiltration, and cytokines like IFN-γ and TNF-α are intimately involved in the pathogenesis of EAN. Interleukin 10 (IL-10) is a T(H)2-type cytokine that suppresses monocyte and T(H)1 cell functions. We examined the effect of recombinant human IL-10 (rHuIL-10) in EAN. When administered from the start of immunization with bovine peripheral myelin emulsified in Freund's complete adjuvant, IL-10 effectively suppressed and shortened clinical EAN. Even when given after Day 12 post immunization (pi) after clinical EAN had been established, IL-10 also effectively suppressed the severity of EAN. Pheripheral nerve myelin antigen-reactive IFN-γ-secreting T(H)1-like cells were decreased in lymph nodes from IL-10-treated compared to control EAN rats. PNS autoantigen-induced T cell proliferation and B cell responses were not affected. P2 protein-reactive IFN-γ, TNF-α, IL-1β, and IL-6 mRNA-expressing lymph node cells were also downregulated in IL-10-treated compared to control EAN rats at Day 14 and 26 pi, while P2-reactive IL-4 mRNA-expressing cells were upregulated throughout treatment. Also, in IL-10-treated EAN rats, upregulated anti-P2 IgG1 and downregulated IgG2a were observed. Our results clearly show that rHuIL-10 can suppress clinical EAN, and this suppression is associated with downregulation of T(H)1 responses and macrophage function and upregulated T(H)2 responses.
UR - http://www.scopus.com/inward/record.url?scp=0030907687&partnerID=8YFLogxK
U2 - 10.1006/clin.1997.4331
DO - 10.1006/clin.1997.4331
M3 - Article
C2 - 9143372
AN - SCOPUS:0030907687
SN - 0090-1229
VL - 83
SP - 117
EP - 126
JO - Clinical Immunology and Immunopathology
JF - Clinical Immunology and Immunopathology
IS - 2
ER -