Exercise During Chemotherapy May Reduce Pain By Strengthening Co-regulatory Couplings In The Cytokine Network

Abstract

PURPOSE: Chemotherapy is hypothesized to cause pain partly via dysregulation of the inflammatory cytokine network - namely, by weakening the normal co-regulatory couplings between concentrations of pro- and anti-inflammatory cytokines. Although research suggests that exercise reduces pain in cancer patients by favorably influencing individual markers of inflammation, no studies have examined whether exercise influences the co-regulatory couplings between concentrations of pro- and anti-inflammatory cytokines. The purposes of this study were to assess how regulation of the inflammatory cytokine network is (1) affected by exercise and (2) related to pain. METHODS: We performed simple network analyses (i.e., correlations matrices) on data from 348 cancer patients enrolled in a randomized trial of chemotherapy plus 6 weeks of moderate-intensity walking and resistance exercise (N = 173) vs. chemotherapy alone (N = 175) in mixed-type, early/mid-stage cancer patients (mean age = 56, 93% female). At pre- and post-intervention, patients (1) provided blood to assess concentrations of IL-1β, IL-6, IL-8, IL-10, IFNγ, and sTNFR1 via ELISA and (2) reported pain in the last 7 days (0=not present, 10=as bad as you can imagine). RESULTS: Compared to chemotherapy alone, exercise plus chemotherapy strengthened the normal co-regulatory couplings between changes in concentrations of several pro- and anti-inflammatory cytokines - specifically, between IL-6 and all other cytokines (p < 0.05) and between IL-10 and all other cytokines (p < 0.05). Among exercise participants, decreased pain was associated with strengthened co-regulatory coupling between changes in concentrations of IL-6 and IL-10 (r = -0.18, p = 0.047). CONCLUSIONS: Exercise strengthened the regulation of the inflammatory cytokine network via strengthened co-regulatory couplings between concentrations of pro- and anti-inflammatory cytokines. The strength of co-regulatory coupling between IL-6 and IL-10 may mediate the beneficial effects of exercise on pain, considering that IL-6 and IL-10 are known to contribute to the physical conditioning effects of exercise. Our novel methods to analyze cytokine data may complement traditional analytic approaches in the investigation of immune-mediated phenomena beyond this study.