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Study · Animal study (in vivo) · mouse · 2023

7 results

Naturally derived cytokine peptides limit virus replication and severe disease during influenza A virus infection.

Harpur CM, West AC, Le Page MA, Lam M, Hodges C, Oseghale O, Gearing AJ, Tate MD

Clinical & translational immunology23 Mar 2023Cited by 8 (Europe PMC)

PMID36969366 (opens in a new tab)PMCIDPMC10034483 (opens in a new tab)DOI10.1002/cti2.1443 (opens in a new tab)PepBankPUB-36969366
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Summary

ObjectivesNovel host-targeted therapeutics could treat severe influenza A virus (IAV) infections, with reduced risk of drug resistance. LAT8881 is a synthetic form of the naturally occurring C-terminal fragment of human growth hormone. Acting independently of the growth hormone receptor, it can reduce inflammation-induced damage and promote tissue repair in an animal model of osteoarthritis. LAT8881 has been assessed in clinical trials for the treatment of obesity and neuropathy and has an excellent safety profile. We investigated the potential for LAT8881, its metabolite LAT9991F and LAT7771 derived from prolactin, a growth hormone structural homologue, to treat severe IAV infection.MethodsLAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.ResultsIn vitro LAT8881 treatment enhanced cell viability, particularly in the presence of cytotoxic stress, which was countered by siRNA inhibition of host lanthionine synthetase C-like proteins. Daily intranasal treatment of mice with LAT8881 or LAT9991F, but not LAT7771, from day 1 postinfection significantly improved influenza disease resistance, which was associated with reduced infectious viral loads, reduced pro-inflammatory cytokines and increased abundance of protective alveolar macrophages. LAT8881 treatment in combination with the antiviral oseltamivir phosphate led to more pronounced reduction in markers of disease severity than treatment with either compound alone.ConclusionThese studies provide the first evidence identifying LAT8881 and LAT9991F as novel host-protective therapies that improve survival, limit viral replication, reduce local inflammation and curtail tissue damage during severe IAV infection. Evaluation of LAT8881 and LAT9991F in other infectious and inflammatory conditions of the airways is warranted.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mice with severe influenza A infection, daily intranasal LAT8881 from day 1 postinfection significantly improved disease resistance.

    In plain wordsIn mice with severe flu, daily LAT8881 into the nose from day 1 after infection improved resistance to disease.

    Peptide
    AOD-9604
    Outcome
    IncreaseInfluenza disease resistance
    Study

    mousen: not reported in source

    severe influenza A virus infection
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    Dose not stated · intranasalAs given in this study (mouse).

    Source sentences

    Summary
    Daily intranasal treatment of mice with LAT8881 or LAT9991F, but not LAT7771, from day 1 postinfection significantly improved influenza disease resistance, which was associated with reduced infectious viral loads, reduced pro-inflammatory cytokines and increased abundance of protective alveolar macrophages.
    1 context sentence
    Summary · context
    LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice with severe influenza A infection, daily intranasal LAT8881 from day 1 postinfection was associated with reduced infectious viral loads.

    In plain wordsIn mice with severe flu, daily LAT8881 into the nose was linked to lower amounts of infectious virus.

    Peptide
    AOD-9604
    Outcome
    DecreaseInfectious viral load
    Study

    mousen: not reported in source

    severe influenza A virus infection
    Outcome group
    Antiviral activity · Infection
    Studied dose
    Dose not stated · intranasalAs given in this study (mouse).

    Source sentences

    Summary
    Daily intranasal treatment of mice with LAT8881 or LAT9991F, but not LAT7771, from day 1 postinfection significantly improved influenza disease resistance, which was associated with reduced infectious viral loads, reduced pro-inflammatory cytokines and increased abundance of protective alveolar macrophages.
    1 context sentence
    Summary · context
    LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mice with severe influenza A infection, daily intranasal LAT8881 from day 1 postinfection was associated with reduced pro-inflammatory cytokines.

    In plain wordsIn mice with severe flu, daily LAT8881 into the nose was linked to lower levels of inflammatory signals.

    Peptide
    AOD-9604
    Outcome
    DecreasePro-inflammatory cytokines
    Study

    mousen: not reported in source

    severe influenza A virus infection
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated · intranasalAs given in this study (mouse).

    Source sentences

    Summary
    Daily intranasal treatment of mice with LAT8881 or LAT9991F, but not LAT7771, from day 1 postinfection significantly improved influenza disease resistance, which was associated with reduced infectious viral loads, reduced pro-inflammatory cytokines and increased abundance of protective alveolar macrophages.
    1 context sentence
    Summary · context
    LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In mice with severe influenza A infection, daily intranasal LAT8881 from day 1 postinfection was associated with increased abundance of protective alveolar macrophages.

    In plain wordsIn mice with severe flu, daily LAT8881 into the nose was linked to more protective lung immune cells.

    Peptide
    AOD-9604
    Outcome
    IncreaseProtective alveolar macrophages
    Study

    mousen: not reported in source

    severe influenza A virus infection
    Outcome group
    Immune response · Immune and inflammation
    Studied dose
    Dose not stated · intranasalAs given in this study (mouse).

    Source sentences

    Summary
    Daily intranasal treatment of mice with LAT8881 or LAT9991F, but not LAT7771, from day 1 postinfection significantly improved influenza disease resistance, which was associated with reduced infectious viral loads, reduced pro-inflammatory cytokines and increased abundance of protective alveolar macrophages.
    1 context sentence
    Summary · context
    LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In mice with severe influenza A infection, LAT8881 combined with oseltamivir phosphate reduced markers of disease severity more than either compound alone.

    In plain wordsIn mice with severe flu, LAT8881 plus oseltamivir lowered disease severity markers more than either one alone.

    Peptide
    AOD-9604
    Outcome
    DecreaseMarkers of disease severity with oseltamivir combination
    Study

    mousen: not reported in source

    severe influenza A virus infection
    Comparator
    LAT8881 alone or oseltamivir phosphate alone
    Outcome group
    Infection and antimicrobial activity · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    LAT8881 treatment in combination with the antiviral oseltamivir phosphate led to more pronounced reduction in markers of disease severity than treatment with either compound alone.
    1 context sentence
    Summary · context
    LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.
  6. 06LabIn vitro (cells)Efficacy outcome

    In vitro, LAT8881 treatment enhanced cell viability, particularly in the presence of cytotoxic stress.

    In plain wordsIn cells, LAT8881 improved cell survival, especially under toxic stress.

    Peptide
    AOD-9604
    Outcome
    IncreaseCell viability under cytotoxic stress
    Study

    n: not reported in source

    Outcome group
    Cell viability and death · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    LAT8881 treatment enhanced cell viability, particularly in the presence of cytotoxic stress
    1 context sentence
    Summary · context
    LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.
  7. 07LabIn vitro (cells)Mechanism

    In vitro, the cell viability benefit of LAT8881 was countered by siRNA inhibition of host lanthionine synthetase C-like proteins.

    In plain wordsIn cells, switching down the host LanCL proteins removed the cell survival benefit of LAT8881.

    Peptide
    AOD-9604
    Outcome
    Not applicableEffect of LanCL siRNA inhibition on LAT8881 cell viability benefit
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Infection
    Studied dose
    Dose not stated

    Source sentences

    Summary
    which was countered by siRNA inhibition of host lanthionine synthetase C-like proteins.
    1 context sentence
    Summary · context
    LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection.

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.

  1. Version 2Current

    9 Oct 2026, 18:17 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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