Oestradiol suppression of delayed-type hypersensitivity in autoimmune (NZB/NZW)F1 mice is a trait inherited from the healthy NZW parental strain.
In this paper we report that treatment with 17 beta-oestradiol depresses cutaneous delayed-type hypersensitivity (DTH) to oxazolone (OXA) in female oophorectomized NZB/W mice. Analysis of the parental strains revealed that this oestrogen-induced inhibition of DTH mice is a trait inherited from the healthy NZW and not from the autoimmune NZB strain. The down-regulating effect of oestradiol on DTH in female NZB/W mice was found both in the sensitization and effector phase of the DTH response. Decreased DTH reactivity to OXA was demonstrated in oophorectomized NZB/W and NZW mice after administration of both low, physiological doses (s.c. injections) and high, pharmacological doses (siliac tube implantation) of oestradiol. In addition, s.c. implantation of testosterone containing siliac tubes suppressed DTH reactivity to OXA in castrated male NZW mice. This down-regulating effect was not found in male NZB or NZB/W mice similarly treated. Serological analysis revealed that high doses of oestradiol increased whereas testosterone depressed the IgG anti-OXA antibody responses in female NZB/W mice. Our results indicate that one possible contribution of the NZW parental strain to the lupus disease in NZB/W mice is a trait of oestrogen sensitivity leading to the acceleration of the autoimmune disease, the latter feature being inherited from NZB mice.
Carlsten
H
H
Department of Medical Microbiology, University of Göteborg, Sweden.
Holmdahl
R
R
Tarkowski
A
A
Nilsson
L A
LA
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D003433:Crosses, Genetic; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D009919:Orchiectomy; D010052:Ovariectomy; D010081:Oxazolone / Q000276:immunology; D012727:Sex Characteristics
D007166:Immunosuppressive Agents; D010081:Oxazolone; D004958:Estradiol