Monocyte

Where it participates (unsigned role)

1. At the end of infusion free serum antibody levels decreased, circulating immune complex levels increased and complement activation was observed, at approximately 1 to 4 hours after end of infusion increased expression of cytokines and chemokines, a 1.5 to 4-fold increase in neutrophil and monocyte counts and a broad activation of innate immune genes were observed, low-antibody subjects with levels below 20 micrograms per millilitre typically showed minimal changes except when their levels rose above 20 micrograms per millilitre after repeated dosing, mild-to-moderate infusion-related reactions occurred in subjects with antibody at or above 20 micrograms per millilitre, and premedications alleviated some of the infusion-related reactions but also inhibited cytokine responses.

   Naturally occurring anti-beta-glucan IgG antibodies → Imprime PGG / BTH1677, a soluble yeast beta-(1->3)/(1->6)-glucan source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   biomarker_context Imported condition classification; unverified.

   evidence_span

   {"source_cache": "artifacts/glucan-research/30988115.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bd9bd1b314472b30b2e3513ecb5e048178de145217473fa87379e0977d21f90d", "start_char": 0, "end_char": 1787, "text_sha256": "bd9bd1b314472b30b2e3513ecb5e048178de145217473fa87379e0977d21f90d"}

   experimental_model

   Single and multiple intravenous infusions in healthy volunteers stratified by pre-treatment antibody level, with and without premedication

   exposure

   Imprime PGG 4 milligrams per kilogram intravenously, with antihistamine and corticosteroid premedication in some subjects

   limitations

   Healthy volunteers and pharmacodynamic endpoints only. Nothing here measures a tumour outcome, so the antibody strata are not validated treatment-selection thresholds.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Human

   plain_language

   Below a certain antibody level almost nothing happened; above it, the drug worked and also caused the infusion reactions.

   primary_references

   [bg-p30988115] Immune Pharmacodynamic Responses of the Novel Cancer Immunotherapeutic Imprime PGG in Healthy Volunteers. (2019). https://pubmed.ncbi.nlm.nih.gov/30988115/ DOI: 10.4049/jimmunol.1801533

   tissue_or_cell_type

   Peripheral blood

   trigger_kind

   biomarker_context Imported condition classification; unverified.

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 281–292

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single and multiple intravenous infusions in healthy volunteers stratified by pre-treatment antibody level, with and without premedication · source_derived_draft · unverified_draft

   ### bg-antibody-level-gates-the-response At the end of infusion free serum antibody levels decreased, circulating immune complex levels increased and complement activation was observed, at approximately 1 to 4 hours after end of infusion increased expression of cytokines and chemokines, a 1.5 to 4-fold increase in neutrophil and monocyte counts and a broad activation of innate immune genes were observed, low-antibody subjects with levels below 20 micrograms per millilitre typically showed minimal changes except when their levels rose above 20 micrograms per millilitre after repeated dosing, mild-to-moderate infusion-related reactions occurred in subjects with antibody at or above 20 micrograms per millilitre, and premedications alleviated some of the infusion-related reactions but also inhibited cytokine responses. Condition category: biomarker_context nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: Below a certain antibody level almost nothing happened; above it, the drug worked and also caused the infusion reactions. organism: Human tissue_or_cell_type: Peripheral blood experimental_model: Single and multiple intravenous infusions in healthy volunteers stratified by pre-treatment antibody level, with and without premedication limitations: Healthy volunteers and pharmacodynamic endpoints only. Nothing here measures a tumour outcome, so the antibody strata are not validated treatment-selection thresholds. exposure: Imprime PGG 4 milligrams per kilogram intravenously, with antihistamine and corticosteroid premedication in some subjects evidence_span: {"source_cache": "artifacts/glucan-research/30988115.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bd9bd1b314472b30b2e3513ecb5e048178de145217473fa87379e0977d21f90d", "start_char": 0, "end_char": 1787, "text_sha256": "bd9bd1b314472b30b2e3513ecb5e048178de145217473fa87379e0977d21f90d"} [bg-p30988115] Immune Pharmacodynamic Responses of the Novel Cancer Immunotherapeutic Imprime PGG in Healthy Volunteers. (2019). https://pubmed.ncbi.nlm.nih.gov/30988115/ DOI: 10.4049/jimmunol.1801533

   Complete structured claim and evidence

2. Network-level integration of transcriptomics and metabolomics data identifies glycolysis, glutaminolysis and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by beta-glucan in monocytes, accumulation of fumarate due to glutamine replenishment of the TCA cycle integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases, fumarate itself induced an epigenetic program similar to beta-glucan-induced trained immunity, and inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by beta-glucan.

   Fumarate → KDM5 histone demethylases source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/glucan-research/27866838.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8", "start_char": 0, "end_char": 1031, "text_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8"}

   experimental_model

   Network integration of transcriptomics and metabolomics with pathway inhibition in monocytes and in mice

   exposure

   Beta-glucan training with inhibition of glutaminolysis and cholesterol synthesis, and fumarate given alone

   limitations

   Fumarate reproducing the epigenetic programme on its own is the strongest part. The link runs through inhibition of a demethylase, which is not the same modification as an acetylation mark.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Human cells and mouse

   plain_language

   A metabolite piles up and jams the enzyme that would strip the marks off, so the marks stay.

   primary_references

   [bg-p27866838] Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. (2016). https://pubmed.ncbi.nlm.nih.gov/27866838/ DOI: 10.1016/j.cmet.2016.10.008

   tissue_or_cell_type

   Monocyte

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 450–461

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Network integration of transcriptomics and metabolomics with pathway inhibition in monocytes and in mice · source_derived_draft · unverified_draft

   ### bg-fumarate-blocks-a-demethylase Network-level integration of transcriptomics and metabolomics data identifies glycolysis, glutaminolysis and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by beta-glucan in monocytes, accumulation of fumarate due to glutamine replenishment of the TCA cycle integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases, fumarate itself induced an epigenetic program similar to beta-glucan-induced trained immunity, and inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by beta-glucan. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: A metabolite piles up and jams the enzyme that would strip the marks off, so the marks stay. organism: Human cells and mouse tissue_or_cell_type: Monocyte experimental_model: Network integration of transcriptomics and metabolomics with pathway inhibition in monocytes and in mice limitations: Fumarate reproducing the epigenetic programme on its own is the strongest part. The link runs through inhibition of a demethylase, which is not the same modification as an acetylation mark. exposure: Beta-glucan training with inhibition of glutaminolysis and cholesterol synthesis, and fumarate given alone evidence_span: {"source_cache": "artifacts/glucan-research/27866838.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8", "start_char": 0, "end_char": 1031, "text_sha256": "c67ca385f9dd5e9e97432aa9141a594b7121acca8eea6eba3d0738fed75deba8"} [bg-p27866838] Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity. (2016). https://pubmed.ncbi.nlm.nih.gov/27866838/ DOI: 10.1016/j.cmet.2016.10.008

   Complete structured claim and evidence

3. Activation of the cholesterol synthesis pathway but not the synthesis of cholesterol itself is essential for training of myeloid cells, rather the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways, statins which block mevalonate generation prevent trained immunity induction, and monocytes of patients with hyper immunoglobulin D syndrome who are mevalonate kinase deficient and accumulate mevalonate have a constitutive trained immunity phenotype at both immunological and epigenetic levels.

   Mevalonate → Trained immunity, an altered response to a later challenge after the first has ended source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/glucan-research/29328908.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03", "start_char": 0, "end_char": 1173, "text_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03"}

   experimental_model

   Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate

   exposure

   Training of myeloid cells with statins to block mevalonate generation, and monocytes from mevalonate kinase deficient patients

   limitations

   The patient arm is a natural experiment in the opposite direction, which is what makes the mevalonate assignment convincing. The statin result is inhibition of an induced laboratory response.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Human

   plain_language

   It is the intermediate and not the cholesterol that does the training, and people who cannot clear that intermediate are permanently trained.

   primary_references

   [bg-p29328908] Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29328908/ DOI: 10.1016/j.cell.2017.11.025

   tissue_or_cell_type

   Monocyte

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 463–474

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate · source_derived_draft · unverified_draft

   ### bg-mevalonate-not-cholesterol-trains Activation of the cholesterol synthesis pathway but not the synthesis of cholesterol itself is essential for training of myeloid cells, rather the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways, statins which block mevalonate generation prevent trained immunity induction, and monocytes of patients with hyper immunoglobulin D syndrome who are mevalonate kinase deficient and accumulate mevalonate have a constitutive trained immunity phenotype at both immunological and epigenetic levels. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: It is the intermediate and not the cholesterol that does the training, and people who cannot clear that intermediate are permanently trained. organism: Human tissue_or_cell_type: Monocyte experimental_model: Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate limitations: The patient arm is a natural experiment in the opposite direction, which is what makes the mevalonate assignment convincing. The statin result is inhibition of an induced laboratory response. exposure: Training of myeloid cells with statins to block mevalonate generation, and monocytes from mevalonate kinase deficient patients evidence_span: {"source_cache": "artifacts/glucan-research/29328908.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03", "start_char": 0, "end_char": 1173, "text_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03"} [bg-p29328908] Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29328908/ DOI: 10.1016/j.cell.2017.11.025

   Complete structured claim and evidence

4. Trained monocytes display high glucose consumption, high lactate production and a high ratio of NAD+ to NADH, reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin through a dectin-1-Akt-HIF-1 alpha pathway, inhibition of Akt, mTOR or HIF-1 alpha blocked monocyte induction of trained immunity whereas the AMP-activated protein kinase activator metformin inhibited the innate immune response to fungal infection, and mice with a myeloid cell-specific defect in HIF-1 alpha were unable to mount trained immunity against bacterial sepsis.

   Glycolysis → Trained immunity, an altered response to a later challenge after the first has ended source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/glucan-research/25258083.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872", "start_char": 0, "end_char": 1225, "text_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872"}

   experimental_model

   Histone modification profiling and genome-wide transcriptome of trained human monocytes, with pathway inhibition and a myeloid conditional knockout

   exposure

   Beta-glucan training with inhibition of Akt, mTOR or HIF-1 alpha, and metformin as an AMPK activator

   limitations

   The metformin result is an experimental inhibition of an induced response, not a clinical interaction study.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Human cells and mouse

   plain_language

   The rewiring costs energy: block the cell from burning glucose the fast way and the training does not take.

   primary_references

   [bg-p25258083] mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. (2014). https://pubmed.ncbi.nlm.nih.gov/25258083/ DOI: 10.1126/science.1250684

   tissue_or_cell_type

   Monocyte

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 437–448

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Histone modification profiling and genome-wide transcriptome of trained human monocytes, with pathway inhibition and a myeloid conditional knockout · source_derived_draft · unverified_draft

   ### bg-training-needs-aerobic-glycolysis Trained monocytes display high glucose consumption, high lactate production and a high ratio of NAD+ to NADH, reflecting a shift in metabolism with an increase in glycolysis dependent on the activation of mammalian target of rapamycin through a dectin-1-Akt-HIF-1 alpha pathway, inhibition of Akt, mTOR or HIF-1 alpha blocked monocyte induction of trained immunity whereas the AMP-activated protein kinase activator metformin inhibited the innate immune response to fungal infection, and mice with a myeloid cell-specific defect in HIF-1 alpha were unable to mount trained immunity against bacterial sepsis. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: The rewiring costs energy: block the cell from burning glucose the fast way and the training does not take. organism: Human cells and mouse tissue_or_cell_type: Monocyte experimental_model: Histone modification profiling and genome-wide transcriptome of trained human monocytes, with pathway inhibition and a myeloid conditional knockout limitations: The metformin result is an experimental inhibition of an induced response, not a clinical interaction study. exposure: Beta-glucan training with inhibition of Akt, mTOR or HIF-1 alpha, and metformin as an AMPK activator evidence_span: {"source_cache": "artifacts/glucan-research/25258083.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872", "start_char": 0, "end_char": 1225, "text_sha256": "68c4cae9a0e4477a52864e63ecaf5ec977752b5d3246a9ba54aa22d160e41872"} [bg-p25258083] mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. (2014). https://pubmed.ncbi.nlm.nih.gov/25258083/ DOI: 10.1126/science.1250684

   Complete structured claim and evidence

5. Mice lacking functional T and B lymphocytes are protected against reinfection with Candida albicans in a monocyte-dependent manner, C. albicans and fungal cell wall beta-glucans induced functional reprogramming of monocytes leading to enhanced cytokine production in vivo and in vitro, the training required the beta-glucan receptor dectin-1 and the noncanonical Raf-1 pathway, and monocyte training by beta-glucans was associated with stable changes in histone trimethylation at H3K4 which suggests the involvement of epigenetic mechanisms.

   Beta-glucan → Trained immunity, an altered response to a later challenge after the first has ended source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/glucan-research/22901542.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "75bc4bedb7017f3d94d8f7441862392ddca229ed16f93eb528d3f9df3da66408", "start_char": 0, "end_char": 1067, "text_sha256": "75bc4bedb7017f3d94d8f7441862392ddca229ed16f93eb528d3f9df3da66408"}

   experimental_model

   Reinfection protection in mice lacking functional T and B lymphocytes, with monocyte reprogramming in vitro and in vivo

   exposure

   Candida albicans and fungal cell wall beta-glucans as the training stimulus, with the first exposure resolved before rechallenge

   limitations

   The Raf-1 dependence belongs to this training protocol. It does not establish that every beta-glucan training protocol is independent of the canonical Syk route.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Mouse

   plain_language

   Animals with no adaptive immune system at all were still protected the second time, because their monocytes had been rewired.

   primary_references

   [bg-p22901542] Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. (2012). https://pubmed.ncbi.nlm.nih.gov/22901542/ DOI: 10.1016/j.chom.2012.06.006

   tissue_or_cell_type

   Monocyte

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 424–435

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reinfection protection in mice lacking functional T and B lymphocytes, with monocyte reprogramming in vitro and in vivo · source_derived_draft · unverified_draft

   ### bg-training-runs-through-raf1 Mice lacking functional T and B lymphocytes are protected against reinfection with Candida albicans in a monocyte-dependent manner, C. albicans and fungal cell wall beta-glucans induced functional reprogramming of monocytes leading to enhanced cytokine production in vivo and in vitro, the training required the beta-glucan receptor dectin-1 and the noncanonical Raf-1 pathway, and monocyte training by beta-glucans was associated with stable changes in histone trimethylation at H3K4 which suggests the involvement of epigenetic mechanisms. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: Animals with no adaptive immune system at all were still protected the second time, because their monocytes had been rewired. organism: Mouse tissue_or_cell_type: Monocyte experimental_model: Reinfection protection in mice lacking functional T and B lymphocytes, with monocyte reprogramming in vitro and in vivo limitations: The Raf-1 dependence belongs to this training protocol. It does not establish that every beta-glucan training protocol is independent of the canonical Syk route. exposure: Candida albicans and fungal cell wall beta-glucans as the training stimulus, with the first exposure resolved before rechallenge evidence_span: {"source_cache": "artifacts/glucan-research/22901542.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "75bc4bedb7017f3d94d8f7441862392ddca229ed16f93eb528d3f9df3da66408", "start_char": 0, "end_char": 1067, "text_sha256": "75bc4bedb7017f3d94d8f7441862392ddca229ed16f93eb528d3f9df3da66408"} [bg-p22901542] Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. (2012). https://pubmed.ncbi.nlm.nih.gov/22901542/ DOI: 10.1016/j.chom.2012.06.006

   Complete structured claim and evidence

6. We identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells, B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8-positive T cell killer function, and in mice B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses.

   B cell → Gamma-aminobutyric acid source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/gaba-research/34732892.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b", "start_char": 0, "end_char": 878, "text_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b"}

   experimental_model

   Identification of a metabolite secreted by activated B cells, with monocyte differentiation and two genetic tests in mice

   exposure

   B cell-derived GABA, with B cell deficiency and B cell-specific inactivation of the GABA-generating enzyme GAD67

   limitations

   The B cell-specific enzyme deletion is what makes the source assignment strong. The enzyme deleted is GAD67, not the GAD65 that is the diabetes autoantigen.

   nutrient_topic

   GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

   organism

   Mouse

   plain_language

   B cells release this molecule into a tumour, where it turns arriving monocytes into cells that shut down the killers.

   primary_references

   [gb-p34732892] B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity. (2021). https://pubmed.ncbi.nlm.nih.gov/34732892/ DOI: 10.1038/s41586-021-04082-1

   tissue_or_cell_type

   B cell, monocyte and tumour

   GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 599–610

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Identification of a metabolite secreted by activated B cells, with monocyte differentiation and two genetic tests in mice · source_derived_draft · unverified_draft

   ### gb-b-cells-secrete-gaba-that-shields-tumours We identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells, B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8-positive T cell killer function, and in mice B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: B cells release this molecule into a tumour, where it turns arriving monocytes into cells that shut down the killers. organism: Mouse tissue_or_cell_type: B cell, monocyte and tumour experimental_model: Identification of a metabolite secreted by activated B cells, with monocyte differentiation and two genetic tests in mice limitations: The B cell-specific enzyme deletion is what makes the source assignment strong. The enzyme deleted is GAD67, not the GAD65 that is the diabetes autoantigen. exposure: B cell-derived GABA, with B cell deficiency and B cell-specific inactivation of the GABA-generating enzyme GAD67 evidence_span: {"source_cache": "artifacts/gaba-research/34732892.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b", "start_char": 0, "end_char": 878, "text_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b"} [gb-p34732892] B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity. (2021). https://pubmed.ncbi.nlm.nih.gov/34732892/ DOI: 10.1038/s41586-021-04082-1

   Complete structured claim and evidence

7. Acetaminophen inhibited lipopolysaccharide-induced whole blood prostaglandin E2 and thromboxane B2 production with half-maximal inhibitory concentrations of 44 and 94 micromolar, at therapeutic concentrations of 100 and 300 micromolar it reduced prostaglandin E2 more than thromboxane B2, but in isolated monocytes both were maximally reduced by only 60%, and at the same concentrations it caused a similar and incomplete inhibition of platelet prostaglandin E2 and thromboxane B2 during whole blood clotting, so that in the presence of plasma the drug almost completely suppressed inducible prostaglandin E2 biosynthesis through effects on both cyclooxygenase-2 and inducible prostaglandin E synthase.

   Paracetamol → Inducible prostaglandin E synthase source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/paracetamol-research/12598417.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5796a25a03c77d12e8376a60aa094e481bd0c2ab58b29ddcb70027ab477b267", "start_char": 0, "end_char": 1894, "text_sha256": "e5796a25a03c77d12e8376a60aa094e481bd0c2ab58b29ddcb70027ab477b267"}

   experimental_model

   Human whole blood and isolated monocytes and platelets with parallel prostaglandin E2 and thromboxane B2 measurement

   exposure

   Acetaminophen at therapeutic plasma concentrations of 100 and 300 micromolar, in whole blood and in isolated cells

   limitations

   The whole blood against isolated cell comparison shows plasma components matter, and measuring two prostanoids in parallel separates the synthase from the downstream synthase. Ex vivo only.

   nutrient_topic

   Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol

   organism

   Human

   plain_language

   In whole blood it nearly abolishes the inflammatory prostaglandin; in isolated cells it manages only sixty per cent.

   primary_references

   [apap-p12598417] Effects of acetaminophen on constitutive and inducible prostanoid biosynthesis in human blood cells. (2003). https://pubmed.ncbi.nlm.nih.gov/12598417/ DOI: 10.1038/sj.bjp.0705078

   tissue_or_cell_type

   Monocytes and platelets

   Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 272–283

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human whole blood and isolated monocytes and platelets with parallel prostaglandin E2 and thromboxane B2 measurement · source_derived_draft · unverified_draft

   ### apap-plasma-changes-the-answer Acetaminophen inhibited lipopolysaccharide-induced whole blood prostaglandin E2 and thromboxane B2 production with half-maximal inhibitory concentrations of 44 and 94 micromolar, at therapeutic concentrations of 100 and 300 micromolar it reduced prostaglandin E2 more than thromboxane B2, but in isolated monocytes both were maximally reduced by only 60%, and at the same concentrations it caused a similar and incomplete inhibition of platelet prostaglandin E2 and thromboxane B2 during whole blood clotting, so that in the presence of plasma the drug almost completely suppressed inducible prostaglandin E2 biosynthesis through effects on both cyclooxygenase-2 and inducible prostaglandin E synthase. Condition category: normal nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: In whole blood it nearly abolishes the inflammatory prostaglandin; in isolated cells it manages only sixty per cent. organism: Human tissue_or_cell_type: Monocytes and platelets experimental_model: Human whole blood and isolated monocytes and platelets with parallel prostaglandin E2 and thromboxane B2 measurement limitations: The whole blood against isolated cell comparison shows plasma components matter, and measuring two prostanoids in parallel separates the synthase from the downstream synthase. Ex vivo only. exposure: Acetaminophen at therapeutic plasma concentrations of 100 and 300 micromolar, in whole blood and in isolated cells evidence_span: {"source_cache": "artifacts/paracetamol-research/12598417.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5796a25a03c77d12e8376a60aa094e481bd0c2ab58b29ddcb70027ab477b267", "start_char": 0, "end_char": 1894, "text_sha256": "e5796a25a03c77d12e8376a60aa094e481bd0c2ab58b29ddcb70027ab477b267"} [apap-p12598417] Effects of acetaminophen on constitutive and inducible prostanoid biosynthesis in human blood cells. (2003). https://pubmed.ncbi.nlm.nih.gov/12598417/ DOI: 10.1038/sj.bjp.0705078

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