Table 1.
rRIC Globally Antagonized Doxorubicin-induced Alteration of Inflammatory Factors
| Vehicle (n = 8) | Dox (n = 8) | Dox/rRIC (n = 8) | p Value | |
|---|---|---|---|---|
| BLC | 23.9 (15.2–28.1) | 52.1 (34.8–108)∗ | 47.6 (33.9–60.4)∗ | 0.004 |
| CD30L | 0.39 (0–1.6) | 0.68 (0–3.0) | 0.22 (0–1.7) | 0.74 |
| Eotaxin | 601 ± 22.6 | 692 ± 17.7 | 746 ± 38.2† | 0.009 |
| Eotaxin-2 | 89.6 (50–127) | 132 (71.5–512) | 129 (118–136) | 0.28 |
| Fas L | 1.9 (0.28–3.6) | 3.5 (1.2–9.1) | 1.8 (0–5.3) | 0.40 |
| G-CSF | 29.4 (17.0–74.0) | 56.1 (18.7–131) | 29.1 (10.4–114) | 0.69 |
| GM-CSF | 3.0 ± 0.46 | 3.5 ± 1.1 | 2.4 ± 0.74 | 0.51 |
| ICAM-1 | 959 ± 144 | 1436 ± 40.9† | 1425 ± 114∗ | 0.016 |
| IFNg | 8.1 (5.6–9.7) | 4.6 (3.3–6.8) | 5.7 (3.2–9.1) | 0.26 |
| IL-1a | 1.4 (0.27–2.5) | 1.4 (0.76–2.7) | 1.7 (1.4–6.4) | 0.39 |
| IL-1b | 13.8 (6.2–16.1) | 6.4 (4.7–12.3) | 11.2 (5.2–17.5) | 0.68 |
| IL-2 | 5.1 (4.1–8.9) | 4.9 (1.0–7.4) | 4.5 (2.5–8.3) | 0.72 |
| IL-3 | 0.32 (0.19–0.50) | 0.16 (0.02–0.25) | 0.02 (0–0.16)∗ | 0.024 |
| IL-4 | 1.8 ± 0.20 | 2.2 ± 0.38 | 1.6 ± 0.43 | 0.85 |
| IL-5 | 5.4 (0–12) | 0.22 (0–7.62) | 1.98 (0–10.8) | 0.78 |
| IL-6 | 3.6 (2.6–6.8) | 4.6 (3.4–14.9) | 3.5 (0.68–6.68) | 0.42 |
| IL-7 | 0 (0–0) | 5.1 (0–57.2)∗ | 0 (0–1.35) | 0.050 |
| IL-10 | 13.2 (7.5–21.9) | 7.3 (2.4–13.3) | 12.8 (7.7–18.6) | 0.34 |
| IL-12p70 | 5.7 (2.6–7.0) | 2.4 (0–4.1) | 1.9 (0–7.4) | 0.14 |
| IL-13 | 3.6 (1.4–10.8) | 10.5 (0–19.9) | 11.7 (2.5–14.5) | 0.67 |
| IL-15 | 0 (0–2.9) | 0 (0–13.1) | 0.78 (0–12.7) | 0.47 |
| IL-17 | 2.6 (2.0–4.1) | 5.5 (3.7–14.6) | 3.8 (3.3–4.6) | 0.08 |
| IL-21 | 0 (0–0.65) | 1.3 (0.56–3.4) | 0.43 (0–2.1) | 0.07 |
| KC | 1.9 (1.6–5.4) | 3.4 (2.4–4.6) | 2.6 (2.0–5.0) | 0.55 |
| Leptin | 283 ± 51.6 | 173 ± 47.5 | 269 ± 41.0 | 0.14 |
| LIX | 67.5 (36.5–88.9) | 57 (49.1–74.4) | 69.4 (49.1–112.0) | 0.80 |
| MCP-1 | 4.9 (3.5–8.4) | 9.6 (6.9–13.4) | 7.6 (6.1–9.2) | 0.18 |
| MCP-5 | 8.1 (5.4–9.5) | 30.3 (17.5–63.0)† | 21.3 (15.6–24.9)† | 0.001 |
| MCSF | 0.38 (0.24–0.65) | 0.37 (0.31–0.63) | 0.66 (0.47–1.00) | 0.28 |
| MIG | 348 ± 93.8 | 273.3 ± 45.4 | 278 ± 55.6 | 0.82 |
| MIP-1a | 2.6 ± 0.22 | 2.0 ± 0.16 | 3.3 ± 0.48‡ | 0.023 |
| MIP-1g | 1,200 (1,120–1,250) | 1,060 (985–1,130) | 1,050 (946–1,160) | 0.050 |
| PF4 | 3,436 ± 105 | 3,212 ± 211 | 3,360 ± 170 | 0.64 |
| RANTES | 2.9 (2.6–3.2) | 3.2 (2.7–3.4) | 2.6 (0.67–3.0) | 0.40 |
| TARC | 4.8 (3.5–6.0) | 7.9 (6.7–8.7)∗ | 5.7 (5.1–7.7) | 0.007 |
| TCA-3 | 10.8 ± 0.36 | 21.2 ± 3.35∗ | 15.5 ± 2.6 | 0.015 |
| TIMP-1 | 365 (301–430) | 1,130 (923–1,260)† | 828 (786–1,100)† | <0.001 |
| TNF-α | 3.8 (1.5–4.8) | 3.7 (1.8–5.4) | 2.1 (1.5–5.3) | 0.95 |
| TNF RI | 998 ± 32.4 | 1,366 ± 46.2† | 1,112 ± 74.7‡ | 0.005 |
| TNF RII | 69.3 (58.4–81.0) | 115 (102–169)∗ | 144 (94.3–186.0)† | 0.009 |
Values are median (interquartile range [Q1 and Q3]) or mean ± SE. Multiplex inflammatory array quantified 40 inflammatory factors, and in 28 factors rRIC abrogated doxorubicin-induced alteration. Concentrations in pg/ml.
BLC = B lymphocyte chemoattractant (CXCL13); CD30L = tumor necrosis factor ligand superfamily member 8 (TNFSF8, CD30 ligand); Fas L = Fas ligand (CD95L, CD178); G-CSF = granulocyte colony-stimulating factor; GM-CSF = granulocyte-macrophage colony-stimulating factor; ICAM = intercellular adhesion molecule (CD54); IFN = interferon; IL = interleukin; KC = keratinocyte-derived chemokine (C-X-C motif chemokine receptor 1, CXCL1); LIX = lipopolysaccharide-induced CXC chemokine; MCP = monocyte chemoattractant protein (CCL2); MCSF = macrophage colony-stimulating factor; MIG = monokine induced by gamma (CXCL9); MIP = macrophage inflammatory protein (CCL3); PF = platelet factor (CXCL4); RANTES = regulated upon activation, normal T cell expressed and secreted (CCL5); TARC = thymus and activation regulated chemokine (CCL17); TCA-3 = CCL1, I-309; TIMP = tissue inhibitor matrix metalloproteinase; TNF = tumor necrosis factor; TNFR = tumor necrosis factor receptor.
p < 0.05.
p < 0.01 versus vehicle.
p < 0.05 versus doxorubicin alone.