Tamoxifen alleviates disease severity and decreases double negative T cells in autoimmune MRL-lpr/lpr mice.
Previous study suggested that MRL-lpr/lpr mice treated with tamoxifen (TAM) had less severe proteinuria, reduced serum titre of anti-dsDNA autoantibodies and an increased survival rate. To investigate further the regulatory mechanisms of TAM on MRL-lpr/lpr female mice, a total dose of 200 microg per mice (5.5 mg/kg) was given every 2 weeks subcutaneously, while the control mice were injected with oil only. After being treated with TAM four times, the mice were killed and cellular functions were evaluated. The TAM-treated groups had smaller sized spleen and lymph nodes. Flow cytometric analysis of splenocytes had a significantly lower percentage of cell number of T cells and double negative T cells (CD4- CD8- T cells). There was no difference in cytokine production (interleukin (IL)-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma)) from splenocytes stimulated with concanavalin A (Con A) or cytokines (IL-6) secreted by peritoneal exudate cells when stimulated with lipopolysaccharide (LPS). However, IL-2 from lymph node cells was significantly higher on TAM-treated mice. Finally, splenocytes or purified T cells stimulated with anti-CD3 antibody plus cross-linking immunoglobulin G (IgG) of the TAM-treated group had higher 3H-incorporation of proliferation assay compared with that of control groups. In vitro study further demonstrated that IL-2-activated proliferation of lymph node double negative (DN) T cells can be inhibited by TAM treatment in a dose-dependent manner. Our finding demonstrated that TAM may potentially influence T cells and modulate the immune function, which offers a novel approach to explore the feasibility of hormone therapy for autoimmune diseases.
Wu
W M
WM
Graduate Institute of Microbiology, College of Agriculture, and Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Suen
J L
JL
Lin
B F
BF
Chiang
B L
BL
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001202:Ascitic Fluid / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D007376:Interleukin-2 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D011507:Proteinuria / Q000188:drug therapy; D013154:Spleen / Q000276:immunology; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013629:Tamoxifen / Q000627:therapeutic use*
D000954:Antigens, Surface; D004965:Estrogen Antagonists; D007376:Interleukin-2; D013629:Tamoxifen