EFFECT OF ESTROGEN ON THE IMMUNE SYSTEM

Hormones, particularly estrogens and androgens, can cause different immune
responses in males and females. Females generally have a more vigorous
immune system than males, and while it is clear that differences in sex
steroids contribute to immunologic differences between the sexes, the
mechanism(s) by which they alter immune responses is unknown. One of the
most dramatic sex-related differences in the immune system is the
disproportionate prevalence of autoimmune diseases in females. For
example, systemic lupus erythematosus (SLE) occurs nine times more
frequently in females than males, and rheumatoid arthritis occurs in
females at a ratio of three to one over males. Understanding the basis for
sex steroid/immune system interactions will greatly elucidate the
pathologic states of autoimmune diseases in particular, and immunology in
general. Although the reported experimental effects of sex steroids on immune
responses vary, estrogens generally increase, and androgens generally
decrease, autoimmune reactions. The nature of the interactions between the
endocrine and immune system, and how these affect disease, has yet to be
determined. In this regard, we intend to address three specific aims: 1.)
Define the immune system cell types responsive to estrogen; 2.) identify
immune effector molecular regulated by estrogen, and 3.) evaluate the
effects of estrogen on an SLE-xenograft mouse model. Different immune cell populations from cultured cell lines and mice will be
examined molecularly for the presence of estrogen receptors. Such cells
will then be manipulated in cell culture to examine the effect of estrogen
treatment on the production of immune effector molecules, such as
interferons and interleukins. These studies will allow identification of
the sex steroid target cells and well as the molecules these hormones may
modulate that could lead to sex-related differences in immune responses.
Finally, an animal model of autoimmunity that allowed the in vivo
manipulation of human SLE lymphoid cells will be examined for possible sex
steroid effects on the transferred disease. To assess these effects,
disease parameters will be measured in SCID mice that received parallel
lymphocyte transfers of human SLE cells, and the effects of estrogen
treatment measured.