The anti-inflammatory protein annexin 1 may protect patients from the detrimental effects of severe inflammatory response syndrome, as reported by researchers at Barts and the London, Queen Mary's School of Medicine and Dentistry.
The paper by Damazo et al., "Critical protective role for annexin 1 gene expression in the endotoxemic murine microcirculation," appears in the June issue of The American Journal of Pathology and is accompanied by a commentary.
Severe inflammatory response syndrome, or SIRS, occurs when the body's response to an overwhelming infection becomes uncontrolled. The very immune response meant to clear the pathogen and its toxins actually causes damage to the host's own tissues when it goes into overdrive, releasing too many immune signals. Thus, the immune response must be carefully controlled to prevent damage to the host.
Damazo et al. studied this balancing act by analyzing the effects of the bacterial toxin LPS on normal and annexin 1 knockout mice. Annexin 1 was chosen because it appears to be involved in the resolution phase of the immune response: its expression on white blood cells impairs their ability to bind blood vessel walls, preventing their transit from the blood to other organs.
When normal mice were treated with LPS, the immune system induced a steady migration of white blood cells from the blood into affected tissues. However, mice deficient for annexin 1 exhibited a dramatic release of white blood cells from blood vessels, ultimately leading to 100% mortality by 48 hours.
The researchers characterized the expression of annexin 1 and found that the gene was activated as early as 1.5 and 6 hours after LPS administration, with levels returning to normal by 24 hours. Higher levels of markers of inflammation, and of organ injury, were measured in annexin 1 deficient animals. Altogether, these findings implied that the protective effects of the annexin 1 pathway were activated in the first few hours following toxin administration. In fact, when annexin 1 knockout mice were given small doses of human recombinant annexin 1 in the first 24 hours following LPS treatment, survival increased to 60%.