Relationship between lymph concentration of cytokines and structural transformations in mesenteric lymph nodes in chemotherapy, surgical treatment, and chemotherapy of experimental breast cancer

The aim of this study was to analyze correlations of the morphometry of mesenteric lymph nodes with cytokine concentrations in thoracic duct lymph in chemotherapy and surgical treatment with subsequent chemotherapy of breast cancer. Methods. Breast cancer was induced by subcutaneous injection of N-methyl-N-nitrosourea 5 times with 7-day intervals, into the region of the 2nd breast on the right. The course of chemotherapy was performed according to the CMF scheme. Correlations between concentrations of 24 cytokines of the lymph and cells of lymph node structural regions were estimated by the Spearman rank correlation coefficient. Results. After chemotherapy for breast cancer compared to untreated breast cancer, morphological transformations in lymph nodes indicated decreased activity of the local immune response. Analysis of correlations between lymph concentrations of cytokines and structural changes in lymph nodes identified relationships aimed at increasing the immunomodulatory and antitumor effects of cytokines. After surgical treatment of breast cancer and subsequent chemotherapy compared to chemotherapy alone, positive correlations were found for immunoblasts with cytokine GRO/KC in germinative centers, for cytokine IL-6 with mitotically dividing cells in germinative centers and medullary cords, for IL-5 with immunoblasts in medullary cords, and for chemokine MIP-1a with mature plasma cells in medullary sinuses. Numbers of immunoblasts and medium and small lymphocytes were increased in germinative centers whereas numbers of small lymphocytes and immature and mature plasma cells were increased in medullary sinuses. Areas of medullary cords and the paracortical zone were increased. Correlations were found for cytokine IL-1α with small lymphocytes, for IL-6 with immunoblasts, for IL-7 and IL-18 with medium lymphocytes, for GRO/KC with immunoblasts, for IL-17 with macrophages in the T-dependent zone, for IL-7 and IL-18 with immunoblasts, for IL-12 with macrophages, and for MIP-1a and MCP-1 with mature plasma cells in medullary sinuses. Conclusion. After surgical treatment of breast cancer and subsequent chemotherapy compared to chemotherapy alone, cytokine concentrations in lymph of the thoracic duct were observed to correlate with morphological changes in mesenteric lymph nodes, which may indicate increased activity of the local immune response.