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Alterations in serum bone biomarkers, blood hematology, and cytokine activity by IL‐10 after radiation and wound trauma. (LB36)
Author(s) -
Swift Joshua,
Smith Joan,
Kiang Juliann
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb36
Subject(s) - rankl , osteoclast , medicine , cytokine , hematology , endocrinology , bone remodeling , osteoprotegerin , interleukin 6 , receptor , activator (genetics)
We have previously demonstrated that non‐lethal, high dose of ionizing radiation when combined with another trauma (i.e. non‐lethal skin wounding), accelerates and prolongs radiation‐induced bone loss for at least 120 days post‐exposure. The purpose of this study was to determine the efficacy of interleukin‐10 (IL‐10), an anti‐inflammatory cytokine, to mitigate or prevent negative effects of radiation and/or radiation combined with skin wounding (combined injury; CI) on biomarkers of bone metabolism, hematology, and cytokine activity. To determine the efficacy of IL‐10 treatment on serum parameters of bone metabolism and hematology after radiation injury (RI), wounding (W), and CI (R+W),16‐week‐old B6D2F1/J female mice were exposed to a sub‐lethal dose of 8 Gy γ radiation followed by skin wounding (W and CI groups only; 15‐20% total body skin surface area), and administered either IL‐10 (15 ng/d, s.c.) or an equal volume of sterile saline (VEH; 0.2 mL) 3x/week. Serum biomarkers were assessed 7 and 30 days after insults and compared to sham controls. RI reduced RBCs, WBCs, lymphocytes, and leukocytes after 7 and 30 days. CI exacerbated these reductions, which changes were mitigated with IL‐10 treatment. RI and CI significantly reduced osteoprotogerin (OPG) and increased tartrate resistant acid phosphatase 5b (TRAP5b; biomarker of osteoclast number) and receptor activator of nuclear factor kappa‐B ligand (RANKL). IL‐10 treatment inhibited reductions in OPG (RANKL antagonist), and increases in TRAP5b and RANKL (key to osteoclast differentiation and activation), resulting in reduced RANKL/OPG ratio. IL‐10 treatment after RI and CI attenuated increases in pro‐inflammatory cytokines that promote osteoclastogenesis (IL‐1β, IL‐6, IL‐9, IL‐17, TNF‐α) and elevated anti‐inflammatory cytokines that inhibit osteoclastogenesis (IL‐3, IL‐10, IL‐13, IFN‐γ). These data demonstrate the beneficial effects of IL‐10 treatment on biomarkers of bone metabolism and inflammation after radiation injury and blast trauma, potentially mitigating the negative effects of these injuries on long‐term skeletal health. Furthermore, it appears that IL‐10 may exhibit this response through an inhibition of pro‐inflammatory cytokines and RANKL activation, ultimately mitigating osteoclast activation.