Serum IL-6 and MCP-1 concentrations in dogs with lymphoma before and after doxorubicin treatment as a potential marker of cellular senescence

Background: Chemotherapy can induce cellular senescence and a secretory phenotype characterized by an increased expression of inflammatory cytokines, such as IL-6 and MCP-1. Increased IL-6 and MCP-1 serum concentrations have been documented in dogs with lymphoma, but no studies have evaluated the effects of chemotherapy on cytokine concentrations. Objectives: To measure IL-6 and MCP-1 in 16 client-owned dogs with lymphoma, at baseline and before and after doxorubicin, as a potential marker for senescence and correlate cytokine concentrations with treatment response and toxicities. Methods: Serum IL-6 and MCP-1 concentrations at baseline, 0-h, 3-h, 6-h, 24-h and 1 week post doxorubicin were measured using a canine ELISA. We hypothesized that IL-6 and MCP-1 concentrations would increase following doxorubicin as a result of induction of cellular senescence. Results: IL-6 concentrations were unchanged from baseline to 0-h but significantly decreased 1 week post doxorubicin (p = 0.001) compared to 0-6 h (p = 0.045) and 24-h (p = 0.001) time points. MCP-1 concentrations significantly decreased from baseline to 0-h (p = 0.003). Compared to 0-6 h, MCP-1 concentrations transiently increased at 24-h (p = 0.001) and decreased at 1 week (p = 0.014) post doxorubicin. Changes in IL-6 and MCP-1 concentrations did not correlate with leukocyte count, response to treatment or chemotherapy toxicities. Conclusions: Changes in IL-6 and MCP-1 concentrations did not support doxorubicin-induced cellular senescence or correlate with leukocyte count, response to treatment or chemotherapy toxicity. However, our results suggest that remission status and doxorubicin treatment may influence cytokine concentrations and future studies are warranted to investigate the role of these cytokines as biomarkers.