Exercise-induced modulation of monocytes in breast cancer survivors

Nasim Khosravi; Erik D Hanson; Vahid Farajivafa; William S Evans; Jordan T Lee; Eli Danson; Chad W Wagoner; Elizabeth P Harrell; Stephanie A Sullivan; Kirsten A Nyrop; Hyman B Muss; David B Bartlett; Brian C Jensen; Shahpar Haghighat; Mahdieh Molanouri Shamsi; Claudio L Battaglini

doi:10.1016/j.bbih.2021.100216

Exercise-induced modulation of monocytes in breast cancer survivors

Brain Behav Immun Health. 2021 Mar 22:14:100216. doi: 10.1016/j.bbih.2021.100216. eCollection 2021 Jul.

Authors

Nasim Khosravi^{1

2}, Erik D Hanson^{1

3}, Vahid Farajivafa^{1

2}, William S Evans¹, Jordan T Lee¹, Eli Danson¹, Chad W Wagoner¹, Elizabeth P Harrell¹, Stephanie A Sullivan¹, Kirsten A Nyrop^{3

4}, Hyman B Muss^{3

4}, David B Bartlett⁵, Brian C Jensen⁶, Shahpar Haghighat⁷, Mahdieh Molanouri Shamsi², Claudio L Battaglini^{1

3}

Affiliations

¹ Department of Exercise & Sport Science, Exercise Oncology Research Laboratory, University of North Carolina, Chapel Hill, NC, USA.
² Physical Education & Sport Sciences Department, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran.
³ Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
⁴ Department of Hematology Oncology University of North Carolina, Chapel Hill, NC, USA.
⁵ Department of Medicine, Duke University, Durham, NC, USA.
⁶ Division of Cardiology, University of North Carolina, Chapel Hill, NC, USA.
⁷ Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Abstract

Background: Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood.

Objectives: The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors.

Methods: Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14⁺CD16^- and CD14⁺CD16⁺ monocytes using flow cytometry.

Results: Exercise training decreased IL-1ß⁺CD14⁺CD16^- proportion (24.6%, p=0.016), IL-1ß⁺CD14⁺CD16^- mean fluorescence intensity (MFI) (-9989, p=0.014), IL-1ß⁺CD14⁺CD16⁺ MFI (-11101, p=0.02), and IL-6⁺CD14⁺CD16^- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14⁺CD16^- (-63, p=0.002) and CD14⁺CD16⁺ (-18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14⁺CD16⁺ concentrations being decreased at 1 h post without changes in intracellular cytokine production.

Conclusions: Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production.

Keywords: Breast cancer; Cytokines; Exercise; Inflammation; Monocyte; Toll like receptor.