Immunoregulation induced by autologous serum collected after acute exercise in obese men: a randomized cross-over trial

Gilson P Dorneles,Simone G Fonseca,Pedro R T Romão,Igor M Da Silva,Viviane R Elsner,Alessandra Peres,Maeli Andressa Santos

doi:10.1038/s41598-020-78750-z

Abstract

In this study, we evaluated the effects of autologous serum collected after two types of exercise on the in vitro inflammatory profile and T cell phenotype of resting peripheral blood mononuclear cells (PBMCs) in obese men. Serum samples and PBMCs were obtained from eight obese men who performed two exercise bouts—high intensity interval exercise (HIIE) and exhaustive exercise session to voluntary fatigue—in a randomized cross-over trial. Pre-exercise PBMCs were incubated with 50% autologous serum (collected before and after each exercise bout) for 4 h. In vitro experiments revealed that post-HIIE serum reduced the histone H4 acetylation status and NF-κB content of PBMCs and suppressed the production of both TNF-α and IL-6 by PBMCs, while increasing IL-10 production. Post-exhaustive exercise serum induced histone H4 hyperacetylation and mitochondrial depolarization in lymphocytes and increased TNF-α production. In vitro post-HIIE serum incubation resulted in an increase in the frequencies of CD4 + CTLA-4 + and CD4 + CD25+ T cells expressing CD39 and CD73. Post-exhaustive exercise serum decreased the frequency of CD4 + CD25 + CD73+ T cells but increased CD4 + CD25-CD39 + T cell frequency. Both post-exercise serums increased the proportions of CD4 + PD-1 + and CD8 + PD-1+ T cells. Blood serum factors released during exercise altered the immune response and T cell phenotype. The type of exercise impacted the immunomodulatory activity of the post-exercise serum on PBMCs.

Highlights

In this study, we evaluated the effects of autologous serum collected after two types of exercise on the in vitro inflammatory profile and T cell phenotype of resting peripheral blood mononuclear cells (PBMCs) in obese men
This report provides the first evidence that systemic factors released into the peripheral blood during different types of exercise bouts differentially change several parameters related to the immune function in the resting PBMCs of obese men
We observed that the inflammatory response and lymphocyte phenotypical markers in PBMCs incubated with post-exercise serum were dependent on the exercise type: (a) post-higher in both post-exercise serum incubation models (HIIE) serum incubation increased the frequencies of CD4 + CD25 + CD39 +, CD4 + CD25 + CD73 +, CD4 + CD25 + CD39 + CD73 +, CD4 + cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) +, and CD8 + PD-1+ T cells and the production of IL-10 concomitant to the decreased NF-κB content, H4ac levels, TNF-α, and IL-6 production in PBMCs and (b) higher TNF-α production and H4ac levels, increased frequencies of CD4 + CD25-CD39 + and CD8 + PD-1+ T cells, and lower proportions of CD4 + CD25CD73+ T cells occurred after the incubation of PBMCs with autologous serum collected after exhaustive exercise

Summary

Introduction

We evaluated the effects of autologous serum collected after two types of exercise on the in vitro inflammatory profile and T cell phenotype of resting peripheral blood mononuclear cells (PBMCs) in obese men. The type of exercise impacted the immunomodulatory activity of the post-exercise serum on PBMCs. Acute endurance exercise elicits a transient increase in the number of peripheral blood mononuclear cells (PBMCs), including T c ells[1]. CD4+ T cells expressing the surface marker cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have strong inhibitory effects on other leukocytes through cell-to-cell interactions[14]. The programmed cell death protein 1 (PD-1) downregulate the immune response and promote self-tolerance by suppressing T cell function[15] In this regard, the increased expression of ectonucleotidases, CTLA-4, and PD-1 is associated with an immunoregulatory, suppressive, and anti-inflammatory p rofile[16]. Chromatin remodeling through histone acetylation impacts the immunoregulatory molecules expressed on the cell surface of lymphocytes, such as CTLA-4, CD39, and CD73 in CD4+ T cells, and histone acetyltransferase overexpression increases PD-1 expression in lymphoid c ells[20,21]

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Conclusion