Women Excluded from Double Dose Endotoxin experiments in Netherlands

2 nanogram/kilogram body weight obviously considered too dangerous in a 2025 study by the same researchers who previously gave 1 nanogram/kilogram body weight to Women. Blood and Bone Marrow sampled

Please see my recent piece on the 110 volunteers in The Netherlands who opened their veins to Endotoxin twice with a 7 day interval.¹

The paper I look at today was kindly brought to my attention by a friend on X.

It looks at the Endotoxin induced Systemic Inflammation and its impairment of Myelopoiesis and Interferon type I responses in Men.

Myelopoiesis definition:

Production of Leukocytes in Blood, such as MONOCYTES and GRANULOCYTES. This process also produces precursor cells for MACROPHAGE and DENDRITIC CELLS found in the Lymphoid tissue.²

Once again the authors fail to mention prior vaccination status of the Men involved, invalidating the study and showing the editors and reviewers of Nature can’t live up to normal academic ethics.

Starting with the end of this second paper³, the authors state:

A limitation of the present study is the use of a male-only study cohort, which limits the ability to apply these findings to female patients.

Females make significantly more proinflammatory cytokines in response to LPS administration than males.

However, despite the sex-based differences in the magnitude of the response, the molecular mechanisms underlying the immune response to LPS are highly conserved and there are no significant differences in the immune-related pathways enriched in both sexes, so this model of systemic inflammation can guide future research in more complex disease models or clinical scenarios in both females and males.

They studied “Healthy” volunteers, compared with Covid19 patients and Sepsis patients.

It is a very long paper, that would take you many hours to wade through, and I found it difficult to choose an illustration. I settled on their Extended Data Figure 1.

Please click to enlarge. They used normal saline as placebo that produced no symptoms because they were preconditioned as in the Women versus Men study.

Kind readers might like to let me know what the intravenous Glucose does ?

Let’s hope none of the volunteers was undiagnosed Diabetic.

Prehydration (1.5 l of 2.5% glucose/0.45% NaCl) was administered intravenously in the hour before the challenge.

Caption reads:

Characterization of LPS-induced systemic inflammation.

a, Box plots of flu-like symptoms, body temperature, and heart rate following intravenous injection of placebo (0.9% NaCl, blue, n = 4) or LPS (2 ng kg−1, red, n = 7) in healthy volunteers.

b, Heatmap of log2(fold-change) blood concentrations of cytokines TNF, IL-10, CCL4, CCL3, IL-6, CXCL8, CCL2, IL-1RN following intravenous injection of placebo (0.9% NaCl, n = 4) or LPS (2 ng kg−1, n = 7) compared with baseline (timepoint 0) in healthy volunteers.

c, Box plots of absolute number of blood leukocytes, monocytes, lymphocytes and neutrophils following intravenous injection of placebo (0.9% NaCl, blue, n = 4) or LPS (2 ng kg−1, red, n = 7) in healthy volunteers.

d, Representative example of flow cytometric analysis of different blood monocyte subsets before (baseline) and at 4 h and d7 following LPS administration (2 ng kg−1). Box plots in a, c shows median, first and third quartiles; whiskers show 1.5x the interquartile range

The authors chose a very small subset of the massive number of Genes dysregulated by Endotoxin, for which I have provided links to the US Comparative Toxicogenomics Database housing links to many thousands of peer-reviewed papers.⁴

As just one example, earlier I mentioned that CCL4 elevation is found with Endotoxin Induced Myocarditis and Fibrosis, so these Men should have been warned as part of Informed Consent.⁵

But were they ? Were they paid to risk their lives and reproductive health ?

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2. https://www.ncbi.nlm.nih.gov/mesh?Db=mesh&Cmd=DetailsSearch&Term=%22Myelopoiesis%22%5BMeSH+Terms%5D

3. Farid Keramati, Guus P. Leijte, Niklas Bruse, Inge Grondman, Ehsan Habibi, Cristian Ruiz-Moreno, Wout Megchelenbrink, Annemieke M. Peters van Ton, Hidde Heesakkers, Manita E. Bremmers, Erinke van Grinsven, Kiki Tesselaar, Selma van Staveren, Walter J. van der Velden, Frank W. Preijers, Brigit te Pas, Raoul van de Loop, Jelle Gerretsen, Mihai G. Netea, Hendrik G. Stunnenberg, Peter Pickkers and Matthijs Kox. April 2025. Systemic inflammation impairs myelopoiesis and interferon type I responses in humans. Nature Immunology. https://doi.org/10.1038/s41590-025-02136-4

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