Expression of Human Interleukin 8 in Mice Alters Their Natural Behaviors

OBJECTIVE: To examine the effects of human interleukin (IL) 8 expression on mouse behavior. METHODS: A mouse line expressing human IL8 in the intervertebral discs (IVD) and cartilaginous tissues (hIL8(+)) was generated. Mouse spontaneous behaviors, including locomotion, climbing, rearing, grooming, eating, drinking, and immobility were recorded with a fully automatic, non-invasive platform. RESULTS: Distance traveled by the hIL8(+) mice declined with age compared with control littermates, and male hIL8(+) mice traveled a shorter distance than male controls and females of either genotype (p <0.05). The hIL8(+) mice also spent less time in locomotion than control mice (p <0.01), and male hIL8(+) mice spent the least amount of time and had lowest count in locomotion compared with the other 3 groups at 12 weeks of age or greater (p <0.05). The hIL8(+) mice spent less time climbing than controls, and male mice spent less time climbing than female mice of the same genotype (p <0.01). The hIL8(+) mice spent more time eating and less time drinking than controls, and all mice spent less time eating and more time drinking with increasing age. Finally, hIL8(+) mice spent more time immobile than controls, and male hIL8(+) mice spent more time immobile than any other group (p <0.05). CONCLUSION: The hIL8(+) mice, especially hIL8(+) males, showed reduced ambulation and climbing. Mice showed age-related decrease in eating and increase in drinking and grooming time that was also influenced by expression of hIL8. These changes in natural behaviors in control mice are consistent with functional decline with age. Effects of hIL8 superimposed on the natural aging process could involve systemic (e.g., on the brain) and local (e.g., in the spine and joint tissues) mechanisms. Future exploration of these mechanisms might be productive.