Stimulation of Brain AMP-Activated Protein Kinase Attenuates Inflammation and Acute Lung Injury in Sepsis.

Mulchandani N, Yang WL, Khan MM, Zhang F, Marambaud P, Nicastro J, Coppa GF, Wang P

Molecular medicine (Cambridge, Mass.)30 Jul 2015Cited by 20 (Europe PMC)

PMID26252187PMCIDPMC4656202DOI10.2119/molmed.2015.00179PepBankPUB-26252187

Summary

Sepsis and septic shock are enormous public health problems with astronomical financial repercussions on health systems worldwide. The central nervous system (CNS) is closely intertwined in the septic process but the underlying mechanism is still obscure. AMP-activated protein kinase (AMPK) is a ubiquitous energy sensor enzyme and plays a key role in regulation of energy homeostasis and cell survival. In this study, we hypothesized that activation of AMPK in the brain would attenuate inflammatory responses in sepsis, particularly in the lungs. Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV. The septic mice treated with AICAR exhibited elevated phosphorylation of AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle. Similarly, the expressions of TNF-α, IL-1β, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced. Moreover, histological findings in the lungs showed improvement of morphologic features and reduction of apoptosis with AICAR treatment. We further found that the beneficial effects of AICAR on septic mice were diminished in AMPKα2 deficient mice, showing that AMPK mediates these effects. In conclusion, our findings reveal a new functional role of activating AMPK in the CNS to attenuate inflammatory responses and acute lung injury in sepsis.

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

Results from this study13

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

01AnimalAnimal study (in vivo)Mechanism
In septic mice, AICAR increased brain AMPKα phosphorylation versus vehicle.
In plain wordsIn mice with sepsis, AICAR increased brain AMPKα phosphorylation versus vehicle.
Peptide
AICAR (acadesine)
Outcome
IncreaseBrain AMPKα phosphorylation
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Receptor activity and mechanism · Immune and inflammation
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
The septic mice treated with AICAR exhibited elevated phosphorylation of AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218701
02AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced serum aspartate aminotransferase versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced blood aspartate aminotransferase versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseSerum aspartate aminotransferase
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Liver fat and liver function · Liver
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
The septic mice treated with AICAR exhibited elevated phosphorylation of AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218702
03AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced serum TNF-α versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced blood TNF-α versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseSerum TNF-α
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
The septic mice treated with AICAR exhibited elevated phosphorylation of AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218703
04AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced serum IL-1β versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced blood IL-1β versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseSerum IL-1β
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
The septic mice treated with AICAR exhibited elevated phosphorylation of AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218704
05AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced serum IL-6 versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced blood IL-6 versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseSerum IL-6
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Inflammation markers · Immune and inflammation
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
The septic mice treated with AICAR exhibited elevated phosphorylation of AMPKα in the brain along with reduced serum levels of aspartate aminotransferase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), compared with the vehicle.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218705
06AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced lung TNF-α expression versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced lung TNF-α expression versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseLung TNF-α expression
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Inflammation markers · Respiratory
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
Similarly, the expressions of TNF-α, IL-1β, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218706
07AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced lung IL-1β expression versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced lung IL-1β expression versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseLung IL-1β expression
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Inflammation markers · Respiratory
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
Similarly, the expressions of TNF-α, IL-1β, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218707
08AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced lung keratinocyte-derived chemokine expression versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced lung keratinocyte-derived chemokine expression versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseLung keratinocyte-derived chemokine
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Inflammation markers · Respiratory
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
Similarly, the expressions of TNF-α, IL-1β, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218708
09AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced lung macrophage inflammatory protein-2 expression versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced lung macrophage inflammatory protein-2 expression versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseLung macrophage inflammatory protein-2
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Inflammation markers · Respiratory
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
Similarly, the expressions of TNF-α, IL-1β, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218709
10AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced lung myeloperoxidase activity versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced lung myeloperoxidase activity versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseLung myeloperoxidase activity
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Inflammation markers · Respiratory
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
Similarly, the expressions of TNF-α, IL-1β, keratinocyte-derived chemokine and macrophage inflammatory protein-2 as well as myeloperoxidase activity in the lungs of AICAR-treated mice were significantly reduced.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218710
11AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR improved lung morphology versus vehicle.
In plain wordsIn mice with sepsis, AICAR improved lung structure versus vehicle.
Peptide
AICAR (acadesine)
Outcome
IncreaseLung morphology
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Lung injury and fibrosis · Respiratory
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
Moreover, histological findings in the lungs showed improvement of morphologic features and reduction of apoptosis with AICAR treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218711
12AnimalAnimal study (in vivo)Efficacy outcome
In septic mice, AICAR reduced lung apoptosis versus vehicle.
In plain wordsIn mice with sepsis, AICAR reduced lung cell death versus vehicle.
Peptide
AICAR (acadesine)
Outcome
DecreaseLung apoptosis
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
Vehicle (normal saline)
Outcome group
Lung injury and fibrosis · Respiratory
Studied dose
20 ng · intracerebroventricular injectionAs given in this study (mouse).
Source sentences
Summary
Moreover, histological findings in the lungs showed improvement of morphologic features and reduction of apoptosis with AICAR treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
Show in the study text Report a problemFND-2625218712

Studies that did not test the peptide alone1

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

13AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In AMPKα2-deficient septic mice, the reported benefits of AICAR diminished.
In plain wordsIn mice with sepsis, AMPKα2 deficiency reduced AICAR's benefits compared with mice without this deficiency.
Peptide
AICAR (acadesine)
Outcome
Not applicableAMPKα2 dependence of benefits
Study
mousen: not reported in source
Cecal ligation and puncture sepsis in adult male C57BL/6 mice
Comparator
AMPKα2-sufficient septic mice
Outcome group
Receptor activity and mechanism · Immune and inflammation
Source sentences
Summary
We further found that the beneficial effects of AICAR on septic mice were diminished in AMPKα2 deficient mice, showing that AMPK mediates these effects.
1 context sentence(design, population, supporting numbers)
Summary · context
Adult C57BL/6 male mice were treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, 20 ng), an AMPK activator, or vehicle (normal saline) by intracerebroventricular (ICV) injection, followed by cecal ligation and puncture (CLP) at 30 min post-ICV.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-2625218713

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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