Maintained pregnancy levels of oestrogen afford complete protection from post-partum exacerbation of collagen-induced arthritis.
Pregnancy is known to influence the course of rheumatoid arthritis (RA) in women, as well as type II collagen-induced arthritis (CIA) in DBA/1 mice. A characteristic feature is the remission during gestation and the exacerbation of the diseases during the post-partum period. In the case of CIA in DBA 1 mice, two hormonal changes have been assumed to be critical for the induction of the post-partum flare: (i) the fall in steroid hormone levels from those present during pregnancy; and (ii) surges of prolactin (PRL) release at and after delivery. Our results show that treatment with oestradiol during a short period immediately after parturition protects the mouse from a post-partum flare of the disease, and that treatment with bromocriptine, a drug known to inhibit the endogenous PRL release, has a significant though less marked effect. Studies of lactating (i.e. animals with physiological stimulation of endogenous PRL release) and non-lactating arthritic mice revealed no clear-cut differences, indicating that PRL is of minor importance for the induction of the post-partum flare. Some steroids other than oestradiol, which may be implicated in the exacerbation of arthritis, namely progesterone and hydrocortisone, had no clinical effect. Analyses of agalactosyl IgG levels in mice with CIA, and anti-collagen II antibodies in sera collected at the end of the experiments revealed no significant differences between the oestradiol and the control groups. The successful oestradiol treatment of the mice indicates that the drop in endogenous oestradiol levels prior to delivery ends the oestrogen-mediated protection against arthritis during pregnancy.
Mattsson
R
R
Department of Molecular Physiology, AFRC Institute of Animal Physiology and Genetics Research, Cambridge, England.
Mattsson
A
A
Holmdahl
R
R
Whyte
A
A
Rook
G A
GA
D000818:Animals; D001168:Arthritis / Q000097:blood / Q000517:prevention & control*; D001971:Bromocriptine / Q000627:therapeutic use; D003094:Collagen; D004958:Estradiol / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D011247:Pregnancy; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000097:blood; D011644:Puerperal Disorders / Q000517:prevention & control*; D011863:Radioimmunoassay; D013256:Steroids / Q000627:therapeutic use
D013256:Steroids; D001971:Bromocriptine; D004958:Estradiol; D011388:Prolactin; D003094:Collagen