API

Event: 1571

Key Event Title

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Decreased IL-1 production

Short name

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Decreased IL-1 production

Biological Context

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Level of Biological Organization
Cellular

Cell term

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Organ term

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Organ term
immune system


Key Event Components

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Process Object Action

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
IL-1 inhibition MolecularInitiatingEvent

Stressors

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI

Life Stages

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Life stage Evidence
All life stages High

Sex Applicability

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Term Evidence
Unspecific High

Key Event Description

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Decreased IL-1 production by macrophages can be induced by suppressed IL-1 b mRNA induction or suppressed maturation of pro-IL-1b which leads to decreased IL-1b secretion. Indeed, dexamethasone significantly suppresses IL-1β mRNA induction by monocytes after LPS stimulation (Finch-Arietta and Cochran 1991). In contrast, minocycline suppresses IL-1 signaling by the inhibition of caspase-1 activation, which is an essential enzyme for maturation of pro- IL-1β and the secretion of mature IL-1β (Vincent and Mohr 2007). Decreased IL-1 production by macrophages


How It Is Measured or Detected

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The inhibition can be measured by quantitating phosphorylated NF-kB or the proteins or mRNA of IL-6 and IL-8 and other IL-1–responsive cytokines or COX-2 produced by IL-1 stimulated macrophages or macrophage cell lines in the presence of inhibitors (Ref).  


Domain of Applicability

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Although sex differences in immune responses are well known (Klein and Flanagan 2016), there is no reports regarding the sex difference in IL-1 production, IL-1 function or susceptibility to infection as adverse effect of IL-1 blocking agent.  Again, age-dependent difference in IL-1 signaling is not known.

The IL1B gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, and frog (https://www.ncbi.nlm.nih.gov/homologene/481), and the Myd88 gene is conserved in human, chimpanzee, Rhesus monkey, dog, cow, rat, chicken, zebrafish, mosquito, and frog (https://www.ncbi.nlm.nih.gov/homologene?Db=homologene&Cmd=Retrieve&list_uids=1849).

These data suggest that the proposed AOP regarding inhibition of IL-1 signaling is not dependent on life stage, sex, age or species.


Evidence for Perturbation by Stressor


Overview for Molecular Initiating Event

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Dexamethasone can suppress phosphorelation of NF-kB or the induction of the proteins or mRNA of IL-1–responsive cytokines or COX-2 by IL-1 stimulated macrophages or macrophage cell lines (Ref).



Chemical:20384 Dexamethasone, minocycline, innamicaldehyde

Dexamethasone is one of the representatives that significantly suppress IL-1β production from monocytes (Finch-Arietta and Cochran 1991). Minocycline also suppress IL-1 signaling by the inhibition of caspase-1 activation, which is an essential enzyme for maturation of pro- IL-1β and the secretion of mature IL-1β(Vincent and Mohr 2007). Recently, it has been reported that cinnamicaldehyde suppresses serum IL-1β level in endotoxin poisoning mice (Xu, et al. 2016). These data suggest that chemicals as well as drugs can suppress IL-1 signaling through their inhibitory effects on IL-1β.


References

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