title: SM934 treated lupus-prone NZB × NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development.
abstract: BACKGROUND
  Artemisinin and its derivatives were reported to possess strong regulatory effects on inflammation and autoimmune diseases. This study was designed to examine the therapeutic effects and underlying mechanisms of SM934, a water-soluble artemisinin analogue, on lupus-prone female NZB × NZW F(1) mice.
  
  
  RESULTS
  NZB/W F(1) mice were treated orally with SM934 for 3 or 6 months respectively to investigate the effect on clinical manifestations and immunological correlates. To further explore the mechanisms of SM934, ovalbumin (OVA)-immunized or interferon (IFN)-γ-elicited C57BL/6 mice were used. In vivo, treatment with SM934 for 3 or 6 months significantly delayed the progression of glomerulonephritis and increased the survival rate of NZB/W F(1) mice. Clinical improvement was accompanied with decreased Th1-related anti-double-strand DNA (dsDNA) IgG2a and IgG3 Abs, serum interleukin (IL)-17, and increased Th2-related anti-dsDNA IgG1 Ab, serum IL-10 and IL-4. SM934 treatment also suppressed the accumulation of effector/memory T cells, induced the apoptosis of CD4(+) T cells, while enhancing the development of regulatory T cells in NZB/W F(1) mice. In addition, SM934 treatment promoted the IL-10 production of macrophages from NZB/W F(1) mice, OVA-immunized C57BL/6 mice and IFN-γ-elicited C57BL/6 mice. In vitro, SM934 enhanced IL-10 production from primary macrophages stimulated with IFN-γ.
  
  
  CONCLUSIONS
  The results of this study demonstrated that artemisinin analogue SM934 had therapeutic effects on lupus-prone female NZB/W F(1) mice by inhibiting the pathogenic helper T cell development and enhancing anti-inflammatory cytokine IL-10 production.
authors.affiliation: Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Hou
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Wan
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.forename: Pei-Lan
authors.initials: PL
authors.lastname: He
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Zhu
authors.forename: Yi-Fu
authors.initials: YF
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zuo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
chemical_list: D037621:Artemisinins; C550182:beta-aminoarteether maleate; D016753:Interleukin-10