Nicotinamide Mononucleotide Administration Triggers Macrophages Reprogramming and Alleviates Inflammation During Sepsis Induced by Experimental Peritonitis.

Cros C, Margier M, Cannelle H, Charmetant J, Hulo N, Laganier L, Grozio A, Canault M

Frontiers in molecular biosciences27 Jun 2022Cited by 25 (Europe PMC)

PMID35832733PMCIDPMC9271973DOI10.3389/fmolb.2022.895028PepBankPUB-35832733

Summary

Peritonitis and subsequent sepsis lead to high morbidity and mortality in response to uncontrolled systemic inflammation primarily mediated by macrophages. Nicotinamide adenine dinucleotide (NAD+) is an important regulator of oxidative stress and immunoinflammatory responses. However, the effects of NAD+ replenishment during inflammatory activation are still poorly defined. Hence, we investigated whether the administration of β-nicotinamide mononucleotide (β-NMN), a natural biosynthetic precursor of NAD+, could modulate the macrophage phenotype and thereby ameliorate the dysregulated inflammatory response during sepsis. For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity. β-NMN was administered for 4 days after CLP and for 3 days post thioglycolate treatment where peritoneal macrophages were subsequently analyzed. In the CLP model, administration of β-NMN decreased bacterial load in blood and reduced clinical signs of distress and mortality during sepsis. These results were supported by transcriptomic analysis of hearts and lungs 24 h post CLP-induction, which revealed that β-NMN downregulated genes controlling the immuno-inflammatory response and upregulated genes involved in bioenergetic metabolism, mitochondria, and autophagy. In the thioglycolate model, a significant increase in the proportion of CD206 macrophages, marker of anti-inflammatory M2 phenotype, was detected on peritoneal exudate macrophages from β-NMN-administered mice. Transcriptomic signature of these macrophages after bacterial stimulation confirmed that β-NMN administration limited the pro-inflammatory M1 phenotype and induced the expression of specific markers of M2 type macrophages. Furthermore, our data show that β-NMN treatment significantly impacts NAD + metabolism. This shift in the macrophage phenotype and metabolism was accompanied by a reduction in phagolysosome acidification and secretion of inflammatory mediators in macrophages from β-NMN-treated mice suggesting a reduced pro-inflammatory activation. In conclusion, administration of β-NMN prevented clinical deterioration and improved survival during sepsis. These effects relied on shifts in the metabolism of organs that face up an increased energy requirement caused by bacterial infection and in innate immunity response, including reprogramming of macrophages from a highly inflammatory phenotype to an anti-inflammatory/pro-resolving profile.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study13

13 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In mice with CLP-induced sepsis, β-NMN decreased blood bacterial load.
In plain wordsIn mice with sepsis, β-NMN reduced bacteria in blood.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseBlood bacterial load
Study
mousen: not reported in source
C57BL6 mice with CLP-induced sepsis
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
Dose not stated · 4 daysAs given in this study (mouse).
Source sentences
Summary
In the CLP model, administration of β-NMN decreased bacterial load in blood and reduced clinical signs of distress and mortality during sepsis.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273301
02AnimalAnimal study (in vivo)Efficacy outcome
In mice with CLP-induced sepsis, β-NMN reduced clinical signs of distress.
In plain wordsIn mice with sepsis, β-NMN reduced clinical distress.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseClinical distress
Study
mousen: not reported in source
C57BL6 mice with CLP-induced sepsis
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated · 4 daysAs given in this study (mouse).
Source sentences
Summary
In the CLP model, administration of β-NMN decreased bacterial load in blood and reduced clinical signs of distress and mortality during sepsis.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273302
03AnimalAnimal study (in vivo)Efficacy outcome
In mice with CLP-induced sepsis, β-NMN reduced mortality.
In plain wordsIn mice with sepsis, β-NMN reduced mortality.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseMortality
Study
mousen: not reported in source
C57BL6 mice with CLP-induced sepsis
Outcome group
Mortality · Whole body
Studied dose
Dose not stated · 4 daysAs given in this study (mouse).
Source sentences
Summary
In the CLP model, administration of β-NMN decreased bacterial load in blood and reduced clinical signs of distress and mortality during sepsis.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273303
04AnimalAnimal study (in vivo)Mechanism
In septic mouse hearts and lungs, β-NMN reduced expression of genes controlling immunoinflammatory responses.
In plain wordsIn mice with sepsis, β-NMN reduced immunoinflammatory gene expression in hearts and lungs.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseImmunoinflammatory gene expression
Study
mousen: not reported in source
C57BL6 mice with CLP-induced sepsis
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
These results were supported by transcriptomic analysis of hearts and lungs 24 h post CLP-induction, which revealed that β-NMN downregulated genes controlling the immuno-inflammatory response and upregulated genes involved in bioenergetic metabolism, mitochondria, and autophagy.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273304
05AnimalAnimal study (in vivo)Mechanism
In septic mouse hearts and lungs, β-NMN increased expression of genes involved in bioenergetic metabolism.
In plain wordsIn mice with sepsis, β-NMN increased bioenergetic metabolism gene expression in hearts and lungs.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseBioenergetic metabolism gene expression
Study
mousen: not reported in source
C57BL6 mice with CLP-induced sepsis
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
These results were supported by transcriptomic analysis of hearts and lungs 24 h post CLP-induction, which revealed that β-NMN downregulated genes controlling the immuno-inflammatory response and upregulated genes involved in bioenergetic metabolism, mitochondria, and autophagy.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273305
06AnimalAnimal study (in vivo)Mechanism
In septic mouse hearts and lungs, β-NMN increased expression of genes involved in mitochondria.
In plain wordsIn mice with sepsis, β-NMN increased mitochondrial gene expression in hearts and lungs.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseMitochondrial gene expression
Study
mousen: not reported in source
C57BL6 mice with CLP-induced sepsis
Outcome group
Mitochondrial function · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
These results were supported by transcriptomic analysis of hearts and lungs 24 h post CLP-induction, which revealed that β-NMN downregulated genes controlling the immuno-inflammatory response and upregulated genes involved in bioenergetic metabolism, mitochondria, and autophagy.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273306
07AnimalAnimal study (in vivo)Mechanism
In septic mouse hearts and lungs, β-NMN increased expression of genes involved in autophagy.
In plain wordsIn mice with sepsis, β-NMN increased autophagy gene expression in hearts and lungs.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseAutophagy gene expression
Study
mousen: not reported in source
C57BL6 mice with CLP-induced sepsis
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
These results were supported by transcriptomic analysis of hearts and lungs 24 h post CLP-induction, which revealed that β-NMN downregulated genes controlling the immuno-inflammatory response and upregulated genes involved in bioenergetic metabolism, mitochondria, and autophagy.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273307
08AnimalAnimal study (in vivo)Mechanism
In mice with thioglycolate-induced peritonitis, β-NMN significantly increased the proportion of CD206 macrophages.
In plain wordsIn mice with peritonitis, β-NMN increased the proportion of CD206 macrophages.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseCD206 macrophage proportion
Study
mousen: not reported in source
thioglycolate-induced sterile peritonitis
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated · 3 daysAs given in this study (mouse).
Source sentences
Summary
In the thioglycolate model, a significant increase in the proportion of CD206 macrophages, marker of anti-inflammatory M2 phenotype, was detected on peritoneal exudate macrophages from β-NMN-administered mice.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273308
09AnimalAnimal study (in vivo)Mechanism
In the mouse peritonitis study, β-NMN significantly altered NAD metabolism.
In plain wordsIn mice, β-NMN significantly altered NAD metabolism.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
Direction not reportedNAD metabolism
Study
mousen: not reported in source
peritoneal macrophages from β-NMN-treated mice
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated · 3 daysAs given in this study (mouse).
Source sentences
Summary
Furthermore, our data show that β-NMN treatment significantly impacts NAD + metabolism.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273311
10LabEx vivo tissueMechanism
In macrophages from treated mice, β-NMN limited the proinflammatory M1 phenotype after bacterial stimulation.
In plain wordsIn isolated mouse macrophages, prior NMN treatment limited the inflammatory M1 profile after bacterial stimulation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseM1 macrophage phenotype
Study
mousen: not reported in source
peritoneal macrophages from β-NMN-treated mice after bacterial stimulation
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated · 3 daysAs given in this study (mouse).
Source sentences
Summary
Transcriptomic signature of these macrophages after bacterial stimulation confirmed that β-NMN administration limited the pro-inflammatory M1 phenotype and induced the expression of specific markers of M2 type macrophages.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273309
11LabEx vivo tissueMechanism
In macrophages from treated mice, β-NMN induced M2 macrophage marker expression after bacterial stimulation.
In plain wordsIn isolated mouse macrophages, prior NMN treatment increased M2 marker expression after bacterial stimulation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseM2 macrophage marker expression
Study
mousen: not reported in source
peritoneal macrophages from β-NMN-treated mice after bacterial stimulation
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated · 3 daysAs given in this study (mouse).
Source sentences
Summary
Transcriptomic signature of these macrophages after bacterial stimulation confirmed that β-NMN administration limited the pro-inflammatory M1 phenotype and induced the expression of specific markers of M2 type macrophages.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273310
12LabEx vivo tissueMechanism
In macrophages from β-NMN-treated mice, phagolysosome acidification decreased.
In plain wordsIn isolated mouse macrophages, prior NMN treatment reduced phagolysosome acidification.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreasePhagolysosome acidification
Study
mousen: not reported in source
macrophages from β-NMN-treated mice
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated · 3 daysAs given in this study (mouse).
Source sentences
Summary
This shift in the macrophage phenotype and metabolism was accompanied by a reduction in phagolysosome acidification and secretion of inflammatory mediators in macrophages from β-NMN-treated mice suggesting a reduced pro-inflammatory activation.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273312
13LabEx vivo tissueMechanism
In macrophages from β-NMN-treated mice, inflammatory mediator secretion decreased.
In plain wordsIn isolated mouse macrophages, prior NMN treatment reduced inflammatory mediator secretion.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseInflammatory mediator secretion
Study
mousen: not reported in source
macrophages from β-NMN-treated mice
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated · 3 daysAs given in this study (mouse).
Source sentences
Summary
This shift in the macrophage phenotype and metabolism was accompanied by a reduction in phagolysosome acidification and secretion of inflammatory mediators in macrophages from β-NMN-treated mice suggesting a reduced pro-inflammatory activation.
1 context sentence(design, population, supporting numbers)
Summary · context
For this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate to induce sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity.
Show in the study text Report a problemFND-3583273313

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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