Decreased expression of the anti-inflammatory cytokine IL-4 in the hippocampus in response to tumours in a mouse model of breast cancer

Abstract

Many cancer survivors, even years after treatment, struggle with cognitive impairment. These people have difficulties with short-term memory, organisational skills, problem-solving and learning and retaining information. When people have cancer, the body starts an inflammatory response which can reach the brain and trigger these symptoms. In this study, we wanted to see if we could predict if this person is at risk of developing cognitive impairment with a tumour biopsy. To test this, we looked at gene expression levels of inflammatory markers in the tumour and the hippocampus. The hippocampus is the brain region most likely to be affected in people with the symptoms of cognitive impairment. We injected mice with cancer cells in breast tissue, and after 19 days, we took the tumour and hippocampus to measure gene expression. We found that the tumour makes pro-inflammatory immune molecules that help them grow. However, we did not observe increased levels of pro-inflammatory cytokines when we examined the hippocampus. Interestingly, we found that these mice made less of the anti-inflammatory molecule IL-4 compared to mice without tumours. This may make the brain less capable of protecting itself against pro-inflammatory molecules. We also measured the size of the tumour and the spleen. The spleen can grow in size if the body is experiencing high levels of inflammation. We found that with a bigger tumour, the spleen is also bigger. This suggests that a bigger tumour creates a higher inflammatory response. We also found that with bigger tumours and bigger spleens, the gene expression of the anti-inflammatory IL-10 is lowered in the hippocampus but higher in the tumour. Thus, based on these findings, the anti-inflammatory molecules could be more informative in predicting or treating cancer-related cognitive impairment instead of the more commonly looked at pro-inflammatory molecules. This research provides insights into the complex relationship between cancer, inflammation, and cognitive impairment. While inflammation in the tumour microenvironment is present, the impact on brain inflammation and cognitive function is not straightforward. Further studies are needed to understand the underlying mechanisms and identify potential therapeutic targets for managing cognitive impairment in cancer patients.