Effects of exercise on inflammation in patients receiving chemotherapy: a nationwide NCORP randomized clinical trial

Abstract

Purpose: A growing body of research suggests that inflammation plays a role in many chemotherapy-related toxicities such as fatigue, anxiety, and neuropathy. Regular exercise can change levels of individual cytokines (e.g., reducing IL-6, increasing IL-10); however, it is not known whether exercise during chemotherapy affects relationships between cytokines (i.e., whether cytokine concentrations change collectively vs. independently). This study assessed how 6 weeks of exercise during chemotherapy affected relationships between changes in concentrations of several cytokines.

Methods: This is a secondary analysis of a randomized trial studying 6 weeks of moderate-intensity walking and resistance exercise during chemotherapy compared with chemotherapy alone. At pre- and post-intervention, patients provided blood to assess serum concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, and IFN-γ, and receptor sTNFR1. We investigated relationships between cytokines using the correlations between changes in cytokine concentrations from pre- to post-intervention.

Results: We obtained complete data from 293 patients (149 randomized to exercise). Exercise strengthened the correlation between concentration changes of IL-10 and IL-6 (r = 0.44 in exercisers vs. 0.11 in controls; p = 0.001). We observed the same pattern for IL-10:IL-1β and IL-10:sTNFR1. Exercise also induced an anti-inflammatory cytokine profile, per reductions in pro-inflammatory IFN-γ (p = 0.044) and perhaps IL-1β (p = 0.099, trend-level significance).

Conclusions: Our hypothesis-generating work suggests that regular exercise during 6 weeks of chemotherapy may cause certain cytokine concentrations to change collectively (not independently). This work enhances our understanding of relationships between cytokines and complements traditional analyses of cytokines in isolation. Future work should test for replication and relationships to patient outcomes.

Trial registration: Clinical Trials.gov, # NCT00924651, http://www.clinicaltrials.gov .

Keywords: Chemotherapy; Cytokine; Cytokine correlation; Cytokine matrix; Cytokine network; Exercise.

Conflict of interest statement

Conflict of interest statement

The authors have no conflict of interest to declare as the research was voluntarily conducted. The authors have full control of all primary data and agree to allow the journal to review the data if requested.

Figures

Figure 1.

CONSORT diagram of study participants.

Figure 2.

Regular exercise during six weeks of chemotherapy increases the correlation between change in IL-6 concentration and change in IL-10 concentration. Each data point shows one participant, with 143 participants randomized to chemotherapy alone (left) and 142 participants randomized to chemotherapy plus exercise (right). Each figure shows the Pearson’s correlation r and the corresponding p-value from a two-tailed test.

Figure 3.

Regular exercise during six weeks of chemotherapy induces greater correlations among changes in cytokine and receptor concentrations. The network diagram shows the correlation strength between changes in each cytokine or receptor concentration (like the one shown in Figure 2, which involves IL-6 and IL-10). Stronger correlations are shown with thicker lines that vary continuously; positive correlations are red, and negative correlations are blue. Each asterisk (*) indicates that the correlation coefficient differs from zero (p<0.05, two-tailed). Each dagger (†) indicates that the correlation coefficient differs by study arm (p<0.05, two-tailed). These data are also shown in Table 2.

Figure 4.

Regular exercise during six weeks of chemotherapy induces an anti-inflammatory state, as evidenced by reduction in IFNγ (p=0.044) and perhaps IL1β (p=0.099, trend-level effect). Sample sizes are provided at the bottom of each figure. Each asterisk (*) indicates that the change in cytokine concentration differs from zero within study arm (p<0.05, two-tailed). Each dagger (†) indicates that the change in cytokine concentration differs by study arm (p<0.05, two-tailed). Error bars are standard errors and units are log10(pg/mL).