Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell-mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice.
Estrogen is known to influence immune responses in healthy subjects in a dichotomous fashion. Thus, in number of previous studies we and others have demonstrated that B cell activities are augmented after exposure to estrogen whereas T cell reactivity is suppressed. Furthermore, it has been shown that this hormone has significant impact on the course of certain human and experimental autoimmune diseases. In this study we report that treatment with physiological doses of estradiol exerts dichotomous effects on different manifestations of the lupus disease in MRL/l mice. On one hand immune complex-mediated glomerulonephritis was significantly accelerated. This outcome was due to polyclonal B cell activation with increased production of antibodies to double-stranded DNA and formation of circulating immune complexes. In contrast, T cell-mediated lesions such as focal sialadenitis, renal vasculitis, and periarticular inflammation were all significantly ameliorated in MRL/l mice exposed to estrogen. Thus, we were able to demonstrate that, within one subject and even within one organ, administration of estrogen leads to differential outcome of SLE morbidity. We propose that the differential effect of estrogen on the manifestations of the autoimmune disease of MRL/l mice is due to its dichotomous effects on B and T cell-mediated immune responses.
Carlsten
H
H
Department of Clinical Immunology, University of Göteborg, Sweden.
Nilsson
N
N
Jonsson
R
R
Bäckman
K
K
Holmdahl
R
R
Tarkowski
A
A
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001402:B-Lymphocytes / Q000187:drug effects*; D004195:Disease Models, Animal; D004958:Estradiol / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy / Q000209:etiology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D012793:Sialadenitis / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000187:drug effects*; D014657:Vasculitis / Q000188:drug therapy*
D004958:Estradiol