The macrophage low-grade inflammation marker sCD163 is modulated by exogenous sex steroids

Holger J Møller,Kristian A Groth,Anders Bojesen,Claus H Gravholt,Christian Trolle,Christian Høst,Henrik H Thomsen,Anne Skakkebæk

doi:10.1530/ec-13-0067

Abstract

Soluble CD163 (sCD163) is a novel marker linked to states of low-grade inflammation such as diabetes, obesity, liver disease, and atherosclerosis, all prevalent in subjects with Turner syndrome (TS) and Klinefelter syndrome (KS). We aimed to assess the levels of sCD163 and the regulation of sCD163 in regards to treatment with sex hormone therapy in males with and without KS and females with and without TS. Males with KS (n=70) and age-matched controls (n=71) participating in a cross-sectional study and 12 healthy males from an experimental hypogonadism study. Females with TS (n=8) and healthy age-matched controls (n=8) participating in a randomized crossover trial. The intervention comprised of treatment with sex steroids. Males with KS had higher levels of sCD163 compared with controls (1.75 (0.47–6.90) and 1.36 (0.77–3.11) respectively, P<0.001) and the levels correlated to plasma testosterone (r=−0.31, P<0.01), BMI (r=0.42, P<0.001), and homeostasis model of assessment insulin resistance (r=0.46, P<0.001). Treatment with testosterone did not significantly lower sCD163. Females with TS not receiving hormone replacement therapy (HRT) had higher levels of sCD163 than those of their age-matched healthy controls (1.38±0.44 vs 0.91±0.40, P=0.04). HRT and oral contraceptive therapy decreased sCD163 in TS by 22% (1.07±0.30) and in controls by 39% (0.55±0.36), with significance in both groups (P=0.01 and P=0.04). We conclude that levels of sCD163 correlate with endogenous testosterone in KS and are higher in KS subjects compared with controls, but treatment did not significantly lower levels. Both endogenous and exogenous estradiol in TS was associated with lower levels of sCD163.

Highlights

The CD163 molecule, expressed by cells of the monocyte lineage, the macrophages, is part of a scavenger system with a high affinity for the hemoglobin–haptoglobin complex
In controls soluble form of CD163 (sCD163) correlated with BMI, lean body mass (LBM), and similar body measures
This study shows that sCD163, as a macrophage-based marker of chronic low-grade inflammation, is elevated in both Turner syndrome (TS) and Klinefelter syndrome (KS)

Summary

Introduction

The CD163 molecule, expressed by cells of the monocyte lineage, the macrophages, is part of a scavenger system with a high affinity for the hemoglobin–haptoglobin complex. It contains nine scavengerreceptor cysteine-rich domains that are located on the extracellular side of the cell membrane (1). 2 : 217 main and well-described functions is the removal of plasma hemoglobin through endocytosis of the very high-affinity complex hemoglobin–haptoglobin, preventing the oxidative stress from free hemoglobin by the release of the free iron, bilirubin, and carbon monoxide. The function of sCD163 is not clear; a role in the elimination of Staphylococcus aureus has recently been described (4) in addition to the findings of antiinflammatory effects through inhibition on T lymphocyte activation and proliferation (2, 3)

Objectives

Methods

Results

Conclusion