Increased interleukin-6 activity associated with painful chemotherapy-induced peripheral neuropathy in women after breast cancer treatment

Abstract

Accumulating evidence suggests that neural-immune interactions are involved in the development of painful chemotherapy-induced peripheral neuropathy, particularly through the increased release of proinflammatory cytokines. The purpose of this study was used to evaluate levels of interleukin [IL]-6 and IL-6 receptors in women with breast cancer after the conclusion of chemotherapy who either had painful symptoms of chemotherapy-induced peripheral neuropathy (CIPN group, N = 20) or did not experience CIPN symptoms (Comparison group, N = 20). CIPN participants had significantly higher levels of IL-6 and soluble IL-6R (sIL-6R) compared to women without CIPN symptoms (P < .001 for both). In addition, soluble gp130, which blocks the IL-6/sIL-6R complex from binding to gp130 within the cellular membrane, was significantly lower (P < .01). Circulating concentrations of sIL-6R were inversely correlated with the density of IL-6R on the cell surface of monocytes in the total sample (r = -.614, P = .005). These findings suggest that IL-6 transsignaling may be an important biological mechanism associated with the persistence of painful CIPN symptoms, with potential implications for symptom management and research.

Figure 1

Mean levels of serum interleukin [IL]-6 in women with painful CIPN (N = 20) and women without CIPN symptoms (Comparison Group, N = 20). Dots represent mean value of Interleukin [IL]-6 measured in serum; error bars represent 95% CI. Mean (SD), [Range] of the painful CIPN group: 2.43 (1.7) pg/mL [1.3–3.8]; Comparison group: 0.92 (0.6) pg/mL [0.4–1.5]. Independent t-test with Bonferroni correction performed to examine difference between groups: (t(38) = −5.6, P < .001).

Figure 2

Mean levels of serum Soluble IL-6R in women with painful CIPN (N = 20) and women without CIPN symptoms (Comparison Group, N = 20). Dots represent mean value of soluble IL-6R (sIL-6R) measured in serum; error bars represent 95% CI. Mean (SD), [Range] of the Painful CIPN group: 41.6 (9.7) ng/mL [31–54]; Comparison group: 30.2 (5.8) ng/mL [22–39]. Independent t-test with Bonferroni correction performed to examine difference between groups: (t(38) = −5.1, P < .001).

Figure 3

Mean levels of serum soluble gp130 in women with painful CIPN (N = 20) and women without CIPN symptoms (Comparison Group, N = 20). Dots represent mean value of soluble gp130 (sgp130) measured in serum; error bars represent 95% CI. Mean (SD), [Range] of the Painful CIPN group: 228.3 (112.7) ng/mL [198–263]; Comparison group: 350.8 (119.9)  ng/mL [290–407]. Independent t-test with Bonferroni correction performed to examine difference between groups: (t(38) = 4.2, P < .01).