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Inflammation amplifies the antitumor cytostasis by human peritoneal macrophages
S Ben-Efraim1, C Tak, M J Fieren
1Department of Pharmacology, Erasmus University, Rotterdam, The Netherlands.
Abstract:
The effect of an inflammatory environment on the antitumor cytostatic ability of human macrophages was examined. Peritoneal macrophages of patients on continuous ambulatory peritoneal dialysis (CAPD) were collected, when CAPD was without complication, during an intercurrent infectious inflammation and after recovery. Inhibition of 3H-thymidine uptake served as a measure of cytostasis by macrophages co-cultured with target murine cells MOPC-315 plasmacytoma, WEHI-3B myelomonocytic leukemia and L929 transformed fibroblasts. Macrophages from inflammatory peritoneum expressed a markedly enhanced cytostasis, irrespective of the nature of the tumor cell. Endotoxin (LPS) challenge of inflammatory macrophages failed to further reinforce the cytostasis towards MOPC-315 plasmacytoma, but reinforced the cytostasis towards WEHI-3B leukemia (sensitive to inhibition by IL-1) and towards L929 (sensitive to TNF alpha). Cytostasis by supernatants of human peritoneal macrophages against L929 was markedly inhibited by anti-rHuTNF alpha and against WEHI-3B by anti-rHuIL-1 beta. The results suggest a link between inflammatory function and antitumor cytostasis by macrophages. This link is constituted by mediators involved in the activation process of macrophages.
Insights
Human macrophages in an inflammatory state show enhanced antitumor abilities. This heightened cytostatic effect against tumor cells is linked to inflammatory mediators, suggesting a key role in cancer immunity.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Macrophages play a crucial role in the immune response.
- The cytostatic and antitumor functions of macrophages are influenced by their environment.
- Continuous ambulatory peritoneal dialysis (CAPD) patients provide a model for studying peritoneal macrophages.
Purpose of the Study:
- To investigate the impact of an inflammatory environment on the antitumor cytostatic capacity of human peritoneal macrophages.
- To determine if inflammatory mediators influence macrophage-mediated tumor cell inhibition.
Main Methods:
- Human peritoneal macrophages were collected from CAPD patients during normal conditions, inflammation, and recovery.
- Macrophage cytostasis was assessed by measuring the inhibition of 3H-thymidine uptake in co-cultured tumor cell lines (MOPC-315, WEHI-3B, L929).
- The effect of endotoxin (LPS) and specific cytokine inhibitors (anti-TNF alpha, anti-IL-1 beta) on macrophage cytostasis was evaluated.
Main Results:
- Macrophages from an inflamed peritoneum exhibited significantly enhanced cytostasis against all tested tumor cell types.
- Endotoxin (LPS) stimulation further enhanced cytostasis against WEHI-3B leukemia and L929 fibroblasts, but not MOPC-315 plasmacytoma.
- Supernatants from inflammatory macrophages showed reduced L929 and WEHI-3B cell growth inhibition when treated with anti-TNF alpha and anti-IL-1 beta, respectively.
Conclusions:
- An inflammatory environment enhances the antitumor cytostatic ability of human peritoneal macrophages.
- This enhanced function is mediated by inflammatory cytokines such as Tumor Necrosis Factor alpha (TNF alpha) and Interleukin-1 beta (IL-1 beta).
- These findings suggest a crucial link between macrophage inflammatory activation and their capacity to inhibit tumor cell growth.