Effect of sex hormones on experimental autoimmune uveoretinitis (EAU).
OBJECTIVE
Sex hormones have been associated with the prevalence, susceptibility, and severity of autoimmune disease. Although the exact mechanism is unknown, sex hormones are reported to influence cytokine production, specifically by affecting the balance of Th1 and Th2 effector cells. We evaluated the effect of estrogen, progesterone, and testosterone in autoimmune uveoretinitis (EAU), a rodent model of human ocular autoimmune disease.


METHODS
Lewis rats implanted with either beta-estradiol (estrogen), 5-dihydrotestosterone (5-DHT), norgestrel (progesterone), or estrogen plus progesterone were immunized with the retinal antigen interphotoreceptor retinoid binding protein (IRBP) peptide. Evaluation of EAU was based on histology of the eyes and measurement of peripheral immunological responses of DTH and lymphocyte proliferation to S-antigen. Quantitative RT-PCR was used to measure IFN-gamma and IL-10 mRNA in the eyes.


RESULTS
In female rats 5-DHT significantly decreased, estrogen slightly enhanced, but progesterone or estrogen + progesterone did not affect EAU. In contrast, in male rats 5-DHT slightly decreased, estrogen moderately decreased, progesterone did not effect, but, estrogen + progesterone slightly decreased EAU. The results correlated with the ocular levels of Th1 (IFN-gamma) and Th2 (IL-10) cytokine messengers.


CONCLUSIONS
The data support the hypothesis that sex hormones may affect autoimmune diseases by inducing changes in the cytokine balance. This suggests that sex hormone therapy could be considered as an adjunct to anti-inflammatory agents to treat ocular autoimmune diseases in humans.
Buggage
Ronald R
RR
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. buggager@nei.nih.gov
Matteson
Dawn M
DM
Shen
De Fen
DF
Sun
Bing
B
Tuaillon
Nadine
N
Chan
Chi-Chao
CC
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D005136:Eye Proteins; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D016056:Immunodominant Epitopes / Q000276:immunology / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012177:Retinol-Binding Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D014605:Uveitis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014611:Vaccination; D000099214:Retinol-Binding Proteins, Interstitial
D013196:Dihydrotestosterone; D004958:Estradiol; D005136:Eye Proteins; D012739:Gonadal Steroid Hormones; D016056:Immunodominant Epitopes; D007371:Interferon-gamma; D016753:Interleukin-10; D011374:Progesterone; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial