IN THE NAME OF GOD,

THE COMPANIONATE THE MERCIFUL

Mahmoud Najafi

Gonadal SteroidsAnd Their Effect On

Immune Function

Gonadal Steroids

AndrogensEstrogensProgesterone

Woman have:

A more vigorous immune responseA more developed thymusHigher immunoglobulin concentrationStrong primary and secondary responsesMore resistance to the induction of

toleranceGreater ability to reject tumor and allograft

A higher female/male susceptibility ratio:

Systemic Lupus Erytematosus(10:1)Rheumatoid Arthritis(4:1)Multiple SclerosisMyasthenia GravisAutoimmune thyroid disease

Gonadal steroids and SLE

Decreased androgen/estrogen ratio (aggravated)– An increase aromatase activity– Pregnancy– Administration of estrogens containing

contraceptives

Increased androgen/estrogen ratio (ameliorated)– A therapeutic effect

Is aggravated by estrogens

Gonadal steroids and RA

Oral contraceptive and Pregnancy– Mitigate the development of the disease

The age of onset of RA in woman is 40-50 (Menopause)

Is ameliorated by estrogens

Animal Models

Female animal– More rapidly reject allograft transplanted– More vigorous immune response

• Humoral immunity• Cell mediated immunity

Female Rats

Administration of testosterone – Largely prevents the onset of autoimmune

disease– Castrated male demonstrate disease

acceleration

Thymectomy – Ablates beneficial effect of testosterone

Androgen and Estrogen binding site

ThymusBone MarrowPeripheral immune system Gonadectomy

– Hyperplasia of the thymus

The administration of exogenous androgen and estrogen– Thymic involution

Progenitor T & B lymphocytes

Sex steroids have receptor– Positive effect on T-cell lymphopoiesis– Negative effect on B-cell lymphopoiesis

• Ovarietomy Increase number of B-cell

T & B lymphopoiesis is suppressed during pregnancy

Influencing the function of mature T and B cells

Estrogen- Increase activity of CD4+ T cells- Decrease activity of CD8+ T cells- enhances IFN-γ (In vitro study)- Treatment by estrogen

• Increase the number of autoreactive immunoglobulin

Androgen- Have receptor on peripheral T and B cells

GnRH

Synthesis within the hypothalamusGnRH RNA has been detected in spleen & thymus T-cell has GnRH receptor

– May be involved in the maturation and senescence cells within the immune system

Pregnancy

Measure of cell-mediated immunity are suppressed

Humoral immunity is preserved or enhancedLevel of variety of cytokine declineElevated level of Glucorticoids

– Potent inhibitory of IFN-γ• Is a powerful abortifacient

Hypersensitivity and Pregnancy

Systemic Lupus Erytematosus – Type III Hypersensitivity – aggravated during the pregnancy

Rheumatoid Arthritis – Type IV Hypersensitivity – suppressed during the pregnancy

Hypersensitivity and Pregnancy

MS− Progesterone- Attenuate disease severity

• Reduce the inflammatory

response • Reduce demyelination in

the spinal cord

Bone metabolism

Estrogens & androgens– Bone protective effect– Decreased of inflammatory cytokines

• TNF• IL-1, IL-6

Bone loss in post-menopausal– Estrogen replacement therapy

Androgens

Anti-inflammatory- Receptors present on immune tissues- Immunosuppressive on both T & B cells- Decrease thymic mass- Suppress antibody response- Increase TGF-β

Estrogens

Pro or Anti-inflammatory (dependent on the disease)- Receptors present on immune tissues- Decrease thymic mass- Inhibit suppressive T-cells- Facilitate T-helper lymphocyte maturation- Stimulate B-cell mediated antibody response

Progesterone

Anti-inflammatory- Receptors present on some immune tissues