The complex role of estrogens in inflammation

Area of Science:

• Immunology
• Endocrinology
• Pharmacology

Background:

• Estrogens exhibit a dual role in immune responses, with observed anti-inflammatory effects in some contexts and pro-inflammatory effects in others.
• This paradox is evident in conditions ranging from chronic inflammatory diseases to trauma/sepsis and autoimmune disorders.

Purpose of the Study:

• To investigate the reasons behind the paradoxical immunomodulatory effects of estrogens.
• To delineate the criteria that influence whether estrogens exert anti-inflammatory or pro-inflammatory actions.

Main Methods:

• This review synthesizes existing literature on estrogen's effects on the immune system.
• It examines factors influencing estrogen's immunomodulatory actions, including immune stimulus, cell types, target organ microenvironment, timing and concentration of administration, estrogen receptor expression, and intracellular metabolism.

Main Results:

• Estrogen's immune effects are highly context-dependent, varying with the nature of the immune stimulus (foreign vs. self-antigens) and the specific immune cells involved.
• Factors such as disease phase, target organ, timing and dose of 17beta-estradiol, estrogen receptor (ER-alpha/beta) expression, and estrogen metabolism significantly modulate its function.
• Interactions with systemic axes like the hypothalamic-pituitary-adrenal axis and nervous systems also influence estrogen's impact.

Conclusions:

• Estrogens possess both anti-inflammatory and pro-inflammatory properties, contingent upon a complex interplay of biological factors.
• A unified understanding of estrogen's role in all inflammatory diseases is not feasible due to the vast variability in immune and repair system responses.