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J Meyers, Epidemiology, University of Washington, Seattle, United States
A Liu, Fred Hutchinson Cancer Research Center, Seattle, United States
A McTiernan, Fred Hutchinson Cancer Research Center, Seattle, United States
M Wener, Laboratory Medicine, University of Washington, Seattle, United States
B Wood, Laboratory Medicine, University of Washington, Seattle, United States
D Weigle, Medicine; Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, United States
B Sorensen, Fred Hutchinson Cancer Research Center, Seattle, United States
Z Chen-Levy, Laboratory Medicine, University of Washington, Seattle, United States
Y Yasui, Public Health Sciences, University of Edmonton, Edmonton, Alberta, Canada
A Boynton, Fred Hutchinson Cancer Research Center, Seattle, United States
J Potter, Epidemiology, University of Washington, Seattle, United States
C Ulrich, Fred Hutchingson Cancer Research Center, Seattle, United States

Correspondence: Cornelia Ulrich, Email: nulrich{at}fhcrc.org

Abstract

Experimental studies and case reports suggest a multifunctional role of leptin in immune function. However, clinical studies of leptin in healthy individuals with a comprehensive assessment of immunity are lacking. This study investigated associations between serum leptin concentrations and multiple biomarkers of cellular immunity and inflammation among 114 healthy postmenopausal, overweight or obese women. Leptin was measured by radioimmunoassay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured by nephelometry. Flow cytometry was used to measure natural-killer-cell cytotoxicity and to enumerate and phenotype lymphocyte subsets. T-lymphocyte proliferation was assessed in response to phytohemagluttinin, as well as to anti-CD3 antibodies by the flow-cytometric cell-division tracking method. Multiple-linear regression analysis with adjustment for confounding factors and log-transformation, where appropriate, was used. Serum leptin concentrations were positively associated with serum CRP, SAA, and IL-6 (p <0.0001, p=0.01, and p=0.04, respectively), more strongly among women with a BMI <30 kg/m2. The associations were attenuated after adjustment for measured body composition, yet remained significant for CRP and SAA. No statistically significant associations were observed between leptin and NK cytotoxicity, lymphocyte subpopulations or T lymphocyte proliferation. This study fills an important gap in knowledge about the relationship between leptin concentrations and immune function in healthy individuals. Findings support an association between serum leptin and the inflammatory proteins CRP and SAA, which appears to be mediated only partly by adipose tissue. Our study does not support a link between leptin and other immune parameters among overweight or obese, but otherwise healthy, postmenopausal women, perhaps because such effects are only present at low or deficient leptin concentrations.