Research press release


Nature Immunology

Cause of immune system paralysis in sepsis identified



Tom van der Poll、Mihai Neteaたちは、細菌性敗血症患者33人、真菌性敗血症患者13人、実験的に軽度の敗血症を誘発する(短期間、インフルエンザに似た症状を引き起こす程度の少量の菌を注射する)ことに同意した健康なボランティア8人と敗血症の実験的マウスモデルについて、白血球の代謝変化を調べた。すると、白血球が細菌や真菌の感染に対して効果的な応答ができないのは、白血球の全般的な代謝活性の極端な低下が原因らしいことが分かった。患者が敗血症から回復した後は、免疫系細胞の代謝活性も正常に戻った。また、γインターフェロン(健全な免疫応答を示す正常な白血球が放出する因子)を投与することにより、真菌性敗血症患者由来の白血球の代謝活性と免疫応答性が回復できることも明らかになった。


New insights into how the immune system can malfunction during sepsis are reported in a paper published online this week in Nature Immunology. The study demonstrates a new approach for reversing the paralysis of the immune system that characterizes the late stages of sepsis.

Commonly acquired in hospitals and frequently fatal, sepsis is caused by bacteria or fungi that enter the bloodstream. Within a few hours of infection, cells of the immune system become hyperactive and then, days later, the immune system often becomes paralyzed, which makes patients susceptible to other infections. However, the role of white blood cells in the immune response during this later stage of sepsis is poorly understood.

Tom van der Poll, Mihai Netea and colleagues investigated metabolic changes in the white blood cells of 33 patients with bacterial sepsis, 13 patients with fungal sepsis, and 8 healthy volunteers who had agreed to undergo a mild form of experimentally induced sepsis (via injection of low dose that causes only short-term, flu-like symptoms), as well as in an experimental mouse model of sepsis. They found that the inability of white blood cells to respond effectively to bacterial or fungal infections seemed to be caused by a drastic reduction in the cells’ overall metabolic activity. After the patients recovered from sepsis, the normal metabolic activity of their cells of the immune system resumed. The team was also able to restore metabolic activity and responsiveness in white blood cells from patients with fungal sepsis by treating them with interferon-γ - a factor released by normal white blood cells responding in a healthy way.

These distinct and modifiable changes in white blood cell metabolism might represent a potential therapeutic target for effective treatment of this severe condition.

doi: 10.1038/ni.3398


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