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Premenopausal Sexual Dimorphism in Lipopolysaccharide-Stimulated Production and Secretion of Tumor Necrosis Factor
GEORGE MOXLEY, ALAN G. STERN, PATRICIA CARLSON, ELOISE ESTRADA, JINFENG HAN, and LINDA L. BENSON
ABSTRACT.
Methods. Healthy volunteers (72 premenopausal female, 159 male, and 62 postmenopausal female) completed questionnaires and gave peripheral blood specimens for whole blood LPS-stimulated TNF assay and for selected hormone levels. TNFab microsatellite markers were genotyped. Results. Mean LPS-stimulated TNF level in the premenopausal female group was 18% lower than the postmenopausal female mean (1579 ± 913 pg/ml compared with 2257 ± 881 in the men and 1965 ± 950 in the postmenopausal women; p < 0.0003 and p 0.058, respectively). Analyzing a subset for which blood counts were obtained, mean stimulated TNF per monocyte was lower in the premenopausal female group than in the postmenopausal female group and appeared lower than in the male group (2.67 ± 1.96 pg/ml per 103 monocytes vs 4.44 ± 2.16 and 3.60 ± 1.40; p = 0.018 and p = 0.12, respectively). Total plasma cortisol was higher in premenopausal women than men, and, in turn, higher in men than postmenopausal women (mean ± SD 16.1 ± 5.7, 12.2 ± 3.6, and 10.4 ± 4.3 µg/dl, respectively; p < 0.05 for each comparison). Using multiple linear regression to correct for covariates and TNF allelic effects, premenopausal status predicted TNF level independently from potential confounders or TNF genetic markers (covariate-adjusted decrement of 408 pg/ml; p = 0.0241). In the male group, total cortisol predicted lower TNF level (coefficient –67.5 pg/ml for each µg/dl cortisol; p = 0.0006 after stepwise selection), but total testosterone had no effect. In premenopausal women, LPS-stimulated TNF was not related to total estradiol, testosterone, or cortisol level. Conclusion. Premenopausal women had a lower mean whole blood LPS-stimulated TNF level than postmenopausal women, but there was no significant relation to total estradiol, testosterone, or cortisol levels in premenopausal women. (J Rheumatol 2004;31:686-94) Key Indexing Terms:
SEX
From the Rheumatology Section, Hunter Holmes McGuire Veterans Administration Medical Center (VAMC); Division of Rheumatology, Allergy and Immunology, Virginia Commonwealth University; and the Laboratory Service, McGuire VAMC, Richmond, Virginia, USA. Supported by NICHD/NIH through a cooperative agreement (U54 HD28934) as part of the Specialized Cooperative Centers Program in Reproduction Research, by the Department of Veterans Affairs Merit Award, the McGuire Research Institute (AR K24 02131) Mid-Career Clinical Investigator Award, Grace Branch Moore-Arthritis Foundation Professorship, Medical College of Virginia Foundation, and Arthritis Foundation Physician Scientist Development Award (Dr. A.G. Stern). G. Moxley, MD, Associate Professor of Internal Medicine and former Chief, Rheumatology Section; A.G. Stern, MD, Postdoctoral Fellow; J. Han, BSN, Laboratory Specialist; L.L. Benson, MPH, Clinical Coordinator, Rheumatology Section, McGuire VAMC; P. Carlson, PhD, Chief of Laboratory Immunology; E. Estrada, BS, Laboratory Specialist, Laboratory Service, McGuire VAMC. Address reprint requests to Dr. G. Moxley, Box 980263, Virginia Commonwealth University, Richmond, VA 23298-0263. E-mail: gmoxley@hsc.vcu.edu Submitted September 27, 2002; revision accepted October 1, 2003. |