# Exercise-enhanced resolution of inflammation

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2020 · $462,462

## Abstract

Abstract:
Frequent physical activity improves cardiovascular health and prolongs life span, whereas physical inactivity is
associated with premature mortality and global burden of chronic disease. The salutary effects of exercise have been
extensively documented in the literature. Exercise promotes skeletal muscle growth, cardiac hypertrophy, and tissue
angiogenesis and it improves cardiovascular disease (CVD) risk factor profile. Nevertheless, the beneficial effects of
exercise extend beyond reduction in CVD risk factors (blood pressure, lipids) involving mechanisms and processes that
remain largely unknown. This lack of mechanistic understanding underlying the salubrious effects of exercise limits its
optimization in healthy individuals, and hinders extension of its benefits to obese and diabetic individuals, who though
are most likely to gain from exercise, cannot exercise or remain impervious to its benefits. Some investigators have
suggested that CVD risk factor-independent effects of exercise may relate to a decrease in inflammation. Inflammation
is a carefully orchestrated systemic response targeted to degrade offending components, clear tissue debris, promote
healing and restore homeostasis. While escalation of inflammation leading to inflammatory cell invasion and cytokine
production has been extensively studied, less is known about how inflammation is resolved. Recent work has shown
that resolution of inflammation is mediated by specialized pro-resolving lipid mediators (SPMs) that limit neutrophil
extravasation, quell inflammatory signaling, and promote macrophage phagocytosis. SPMs are necessary and sufficient
to resolve inflammation by binding to cognate G-protein coupled receptors (GPCRs). We propose that the beneficial
effects of exercise relate to its ability to promote resolution of inflammation by stimulating the synthesis of pro-resolving
SPMs. Our preliminary data show that exercise-adapted mice display enhanced SPM synthesis, accelerated neutrophil
clearance and increased macrophage phagocytosis, suggesting that exercise exerts beneficial effects on resolution of
inflammation. We also find that catecholamines, which are transiently elevated by exercise, activate SPM biosynthesis
in macrophages and increase 5-lipoxygenase (5-LO) and 12/15-lipoxygenase (15-LO), enzymes that synthesize SPMs.
These observations link processes activated by exercise to key components of inflammation-resolution and have led us
to formulate the hypothesis that exercise-mediated production of catecholamines increases pro-resolving lipid mediator
synthesis and enhances resolution of inflammation. The specific aims are: (1) Determine the effect of exercise on
resolution; (2) Delineate the contribution of catecholamines in mediating the effect of exercise on resolution of
inflammation; (3) Elucidate the role of SPMs in exercise-enhanced resolution. Results of this project will generate new
insights into how exercise regulates inflammation; which processe...

## Key facts

- **NIH application ID:** 9932457
- **Project number:** 5R01GM127495-03
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Jason L Hellmann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $462,462
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932457

## Citation

> US National Institutes of Health, RePORTER application 9932457, Exercise-enhanced resolution of inflammation (5R01GM127495-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9932457. Licensed CC0.

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