Loss of IL-10 Decreases Mouse Postpubertal Mammary Gland Development in the Absence of Inflammation

Abstract

IL-10 is a pleiotrophic anti-inflammatory cytokine. Decreased IL-10 expression is associated with an increased breast cancer risk but the mechanism is not clear. This study was designed to test the hypothesis that the loss of IL-10 alters mammary development, even in the absence of inflammation. Wild-type and IL-10−/− mouse littermates were similar in growth, development, and breeding success. Using whole-mounts and paraffin sections, mammary glands from pre-pubertal mice (d21) were found to not be affected by the IL-10 null genotype. However, after the onset of estrous cycling, ductal structure, but not lymph nodes or adipocytes, of IL-10 knockout mice were found to moderately decrease at day 55, 80, and 150 of age. This phenotype was not rescued by lactogenesis. At day 2 of lactation, IL-10 null mice had reduced lobular complexity and glandular area with the retention of adipocytes. These results support the hypothesis that absence of IL-10 reduces glandular development during postnatal development, at maturity, and during the early stages of lactation. Although our study cannot distinguish between a direct IL-10 effect on the epithelial cells and an indirect systemic effect, epithelial cell responses to IL-10 should be considered in the therapeutic applications of cytokines or cytokine ablation.

• IL-10
• Mammary gland
• Development
• Lactation

ACKNOWLEDGEMENT

This work was supported by an U.S. Army Breast Cancer Concept Award W81XWH0610645 to S-MK. The authors would like to thank University at Buffalo Histology Service Laboratory for the excellent preparation of paraffin sections and for their assistance in acquiring the digitized image files for the whole-mount preparations.