Inflammation in Mice Shown Irrelevant to Human Inflammatory Process

Despite the failure of 150 clinical trials of agents to block inflammatory responses in humans, investigators and regulators still assume that animal research is relevant. A study that compared inflammation-related gene expression between mouse and human has found almost nothing in common.

A recent study in the Proceedings of the National Academy of Sciences (PNAS) concludes that mice and people have little in common when it comes to inflammation -- and that the study of inflammatory conditions would be better served by translational medical research focusing on these complex reactions in actual humans, rather than relying on murine models.

Despite the failure of 150 clinical trials of agents to block inflammatory responses in critically ill patients and the lack of systemic evidence, the PNAS paper finds that investigators and regulators still assume that animal research results mimic the human condition.

The current study evaluated data from multiple studies conducted by the Inflammation and Host Response to Injury Large Scale Collaborative Research Program, including genome-wide responses of white blood cell samples from human volunteers and samples from mouse models.
In humans, leukocyte genomic responses were similar across a number of inflammatory responses to trauma such as burns or sepsis, suggesting the potential for agents to treat a wide range of conditions. But when researchers compared altered gene responses in humans over varying time spans to white blood cell gene expression in mouse models, surprisingly they found almost no similarities.

The difference could be due to underlying biology and/or evolutionary factors affecting tolerance and resistance to infection; the report notes that mice are often more resilient to inflammatory challenges than people are.

The researchers suggest new approaches to improve current models, for example by first requiring comprehensive genomic descriptions in patient studies to define disease,  then using those as a guide for developing animal models.

However, the scientists conclude that their findings challenge the use of murine models. They suggest such models should act as a complement to human studies of inflammation, rather than continuing to serve as the cornerstone of biomedical research in disease discovery and drug development.

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