sepsis, innate immunity, neutrophils, neutrophil extracellular traps, female hormones

Emergency and Intensive Care Medicine

There are gender differences in sepsis prognosis, with male hormones worsening the prognosis and female hormones improving the prognosis. On the other hand, one of the neutrophil functions that contributes to septic organ damage and disseminated intravascular coagulation (DIC) is the overproduction of neutrophil extracellular traps (NETs), and there are reports that NETs formation is involved in the aggravation of recent COVID-19 pneumonia.
We have demonstrated that equol, a female hormone analogue, suppresses NETs in human neutrophils while maintaining neutrophil phagocytic function. Equol is a female hormone analogue derived from soybeans, is relatively inexpensive to produce, and is easily metabolized. In addition, its female hormone-like effects are smaller than those of estradiol, so it is considered to be very safe in terms of side effects.

Focusing on gender differences in sepsis prognosis and applying equol, a female hormone analogue, to sepsis treatment

While hyperactivation of neutrophils (increase in NETs) can contribute to the worsening of pathological conditions, such as organ damage and increased thrombosis, neutrophils are essential cells for infection defense, and prolonged inhibition of their function may be detrimental to the pathological condition.
For this reason, equol, which is easily metabolized and relatively inexpensive to produce as it is derived from soybeans, may be useful as a method of preventing worsening prognosis in acute disease states, not as a drug that produces a rapid effect, but rather to maintain a baseline for improvement of the pathological condition.

Not only in sepsis, but also in autoimmune diseases and COVID-19 pneumonia, the involvement of an increase in NETs due to excessive immunity has been suggested.
We have obtained data showing that equol reduces the growth of NETs, which is expected to lead to the resolution of the above issues.

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1. Michiko Ishikawa, Hayato Yamashita, Nobuki Oka, Takahiro Ueda, Keisuke Kohama, Atsunori Nakao, Joji Kotani. Antithrombin III improved neutrophil extracellular traps in lung after the onset of endotoxemia. JOURNAL OF SURGICAL RESEARCH. 2017. 208. 140-150
2. Michiko Aoyama, Joji Kotani, Makoto Usami. GENDER DIFFERENCE IN GRANULOCYTE DYNAMICS AND APOPTOSIS AND THE ROLE OF IL-18 DURING ENDOTOXIN-INDUCED SYSTEMIC INFLAMMATION. SHOCK. 2009. 32(4). 401-409
3. Ishikawa, M.; Murakami, H.; Kohama, K.; Kuwahara, M.; Hirata, J.; Kotani, J. [Crosstalk between coagulation and inflammation] Suppression of NETs by anticoagulant therapy. ICU and CCU. 2021. 45.(6). 351-355