Open AccessSexual dimorphism in innate immunity
Author(s) -
Moxley George,
Posthuma Danielle,
Carlson Patricia,
Estrada Eloise,
Han Jinfeng,
Benson Linda L.,
Neale Michael C.
Publication year - 2002
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(200201)46:1<250::aid-art10064>3.0.co;2-t
Subject(s) - medicine , allele , analysis of variance , sexual dimorphism , immunology , immunity , biology , endocrinology , immune system , genetics , gene
Objective To establish whether variation in innate immunity, as measured by the level of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)‐stimulated whole‐blood culture, is related to sex or HLA. Methods Normal volunteers (72 women, 159 men) completed questionnaires and donated peripheral blood specimens. Blood samples were exposed to LPS in a 4‐hour in vitro culture, and supernatants were then tested by sandwich‐type immunoassay measuring TNF levels. Statistical techniques included multivariate analysis and maximal‐likelihood modeling of allelic effects. Results Both male and female groups showed substantial within‐group variation (coefficient of variation 59.1% for women, 40.3% for men). However, the mean ± SD LPS‐stimulated TNF level in the female group was nearly 30% lower than in the male group (1,556 ± 919 pg/ml versus 2,203 ± 889 pg/ml; P < 0.0001, unadjusted for covariates). Sex was independent of any microsatellite marker allele of TNF (covariate‐adjusted increment of 785 pg/ml from female to male sex; P < 0.0001). In multivariate modeling of the female group, the LPS‐stimulated TNF level was not independently influenced by menstrual cycle phase, oral contraceptive use, or plasma estradiol level. Allelic modeling showed that significant TNFab microsatellite allelic effects existed ( P = 0.002 versus model omitting allelic effects). The female group showed a significantly downward deviation from mean TNF level with TNFa4b5 (−903 pg/ml deviation from the overall mean) and an upward deviation with TNFa10b4 (598 pg/ml). The male group showed significantly higher‐than‐mean levels with TNFa1b5 (909 pg/ml), TNFa5b7 (1,191 pg/ml), and TNFa6b5 (332 pg/ml). Thus, the two sex groups differed in which of their TNFab marker alleles showed significant deviations from the overall mean. Conclusion Female subjects have a nearly 30% lower innate immune response, stemming largely from influence independent of the HLA‐region TNF locus and without further independent variation stemming from plasma estrogen level.