Maximal Exercise Alters the Inflammatory Phenotype and Response of Mononuclear Cells.

Purpose: Monocytes express the CD14 receptor that facilitates lipopolysaccharide (LPS) ligation to toll-like receptor 4 (TLR4) to elicit production of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-[alpha]). However, pro-inflammatory conditions, such as strenuous exercise, increase the percentage of monocytes expressing CD16, a receptor that enhances LPS stimulated TNF-[alpha] production. Therefore, we examined whether maximal treadmill exercise would alter the inflammatory phenotype of classical (CD14+/CD16-) and pro-inflammatory monocytes (intermediate [CD14++/CD16+] and non-classical [CD14+/CD16++]), evidenced by changes in TLR4, CD14, and CD16 receptor expression, and their inflammatory response to ex vivo LPS stimulation. Methods: Human mononuclear cells from 25 male participants (age: 24.2 +/- 4.0 yr.) were isolated prior to and following exercise to assess TLR4, CD14, and CD16 expression by flow cytometry and ex vivo production of LPS-stimulated inflammatory cytokines (IL-6, IL-10, and TNF-[alpha]). Results: Exercise reduced the percentage of classical monocytes and increased the percentage of intermediate and non-classical monocytes. In addition, TLR4 expression decreased on classical and intermediate monocytes, but not the non-classical monocyte subset. Furthermore, while CD14 expression decreased on all monocyte subsets, CD16 expression increased on intermediate monocytes only. In parallel with these phenotypic changes, the inflammatory milieu shifted towards a pro-inflammatory response following LPS stimulation (decreased IL-6 and IL-10 and increased IL-6 to IL-10 ratio and TNF-[alpha] production). Conclusion: These findings demonstrate that acute maximal exercise elicits a pro-inflammatory phenotype of isolated monocytes exposed to LPS and highlight potential mechanisms that will help elucidate the role of acute and chronic exercise on the innate immune response of circulating monocytes. (C) 2017 American College of Sports Medicine

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