Background: Insulin has been one of the immense contributions to human health. Besides its role in treatment of diabetes, insulin affects inflammatory cytokine production, chronic inflammation and cancer development. We have examined the effect of insulin on cytokine production by human peripheral blood mononuclear cells (PBMC) and its role in the balance between immune and human colon cancer cells.
Methods: Human LPS stimulated and non-stimulated PBMC, HT-29 and RKO cancer cell lines were separately incubated with insulin at various concentrations and the production of TNFα, IL-1β, IL-6, IFNγ, IL-1ra and IL-10 was examined. In addition, the effect of insulin on the secretion of these cytokines by PBMC co-incubated with carcinoma cells was evaluated.
Results: Insulin added to non-stimulated PBMC caused a decreasaed secretion of the pro-inflammatory TNFα. Stimulation of PBMC with either LPS or PMA resulted in decreased production of IL-1β, TNFα and IFNγ and an increased generation of IL-6. The production of the anti-inflammatory cytokine IL-10 was elevated by both stimulated and unstimulated PBMC. Insulin added to PBMC inhibited the secretion of IFNγ stimulated with both HT-29 and RKO cells and reduced TNFα production induced by RKO cells.
Conclusions: The results indicate that insulin interferes with inflammatory cytokine production by stimulated PBMC and it affects the cross talk between immune and colon cancer cells. It appears that the effect of insulin on the immune balance between mononuclear and malignant cells depends on its concentration and type of cancer cells. The findings provide and additional way for understanding the relation between insulin and cancerogenesis.
Author(s): Hanna Bessler and Meir Djaldetti