Disassociation of sex hormone levels and cytokine production in SLE patients.
This study examines whether changes in the cytokine milieu of patients with systemic lupus erythematosus (SLE) are associated with abnormal levels of sex hormone levels in serum. The concentration of 17beta-estradiol (E2), progesterone (Pg) and dehydroepiandrosterone-sulphate (DHEAS) was monitored in sera from 128 lupus patients and 96 controls, and correlated with the activity of their cytokine secreting cells. Results indicate that SLE patients have (i) significantly fewer cells secreting IFNgamma, (ii) increased serum E2 and Pg levels, and (iii) reduced serum DHEAS levels compared to normal controls. However, the observed abnormalities in the cytokine milieu of SLE patients did not correlate with abnormalities in serum sex hormone levels. Instead, the association between IFNgamma production and DHEAS levels evident in healthy controls is absent in SLE patients, suggesting that cells from lupus patients are defective in their ability to produce IFNgamma in response to physiologic stimuli. Similarly, the normal correlation between IL-4 production and E2 levels was lost in patients with severe disease. Thus, while it remains possible that increased E2 and reduced DHEAS levels in lupus patients may help induce cytokine abnormalities early in disease, the subsequent cytokine imbalance does not correlate with sex hormone levels.
Verthelyi
D
D
Retroviral Immunology Section, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA. verthelyi@CBER.FDA.GOV
Petri
M
M
Ylamus
M
M
Klinman
D M
DM
D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism; D011374:Progesterone / Q000097:blood
D016207:Cytokines; D012739:Gonadal Steroid Hormones; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D011374:Progesterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D007371:Interferon-gamma