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

Abstract

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 24h (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 doxorubicininduced 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.

A chronic wound model to investigate skin cellular senescence

“…For example, TGF-β has been demonstrated to induce senescence and senescence-related characteristics in fibroblasts [ 39 ]. Similarly, MCP has been shown to be a SASP-related protein [ 40 ]. We found significantly elevated Mmp3 , Mmp9 , Mcp , and TGF-β mRNA levels in chronic wounds ( Figure 1F ), potentially contributing to the increased senescent cell abundance in chronic wounds.…”

Nanotherapy: New Approach for Impeding Hepatic Cancer Microenvironment via Targeting Multiple Molecular Pathways

“…In the current research, DOX administration in HCC bearing rats induced insignificant reduction in serum CCL2 level paralleled by insignificant down-regulation in CCL2 gene expression level in the liver. Evans et al (2022) demonstrated a significant increase in CCl2 (MCP-1) serum cytokine concentration at 24 h and a significant decrease at 1 week past DOX when compared to the 0-to 6 h time point. Comparing 24 h and 1 week post DOX, there was a significant decrease in CCL2 (MCP-1) cytokine concentrations in dogs with lymphoma.…”