API

Event: 986

Key Event Title

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Increase, Increased susceptibility to infection

Short name

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Increase, Increased susceptibility to infection

Biological Context

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Level of Biological Organization
Individual



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 AdverseOutcome

Stressors

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Taxonomic Applicability

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Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI
Mus musculus Mus musculus 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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Complications from infection as a side-effect of administering FK506 was found to be similar to that of cyclosporin A (Ekberg et al. 2007), and recipients of liver transplants treated with FK506 were found to have suffered bacterial, viral, and fungal infections (Alessiani et al. 1991, Fung et al. 1991).

 

Defect of IL-1 signaling caused by knockout of mice gene or administration of IL-1 receptor antagonist or neutralizing antibodies to human leads to the increased susceptibility to infection. Moreover, polymorphism of IL-1b or IL-1Ra leads to the increased susceptibility to tuberculosis or fungal infection.


How It Is Measured or Detected

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By comparison of the incidence of infection between individuals exposed to stressors and non-exposed individuals.


Domain of Applicability

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The increased susceptibiity to infection caused by IL-1RA or anti-IL-1 antibody has been reported in bothe humans and mice.


Evidence for Perturbation by Stressor



Regulatory Significance of the Adverse Outcome

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A well-functioning immune system is essential for maintaining the integrity of an organism. Immune dysregulation can have serious adverse health consequences, ranging from reduced resistance to infection and neoplasia to allergic and autoimmune conditions. Environmental contaminants, food additives, and drugs can target the immune system, resulting in immune dysregulation. Accordingly, the potential for immunotoxicity, which is defined as the toxicological effects of xenobiotics on the function of the immune system, has raised serious concerns from the public as well as regulatory agencies. Currently, the assessment of chemical immunotoxicity relies mainly on animal models and assays that characterize immunosuppression and sensitization. However, animal studies have many drawbacks, such as high cost, ethical concerns, and questionable relevance to risk assessment for humans.

The immune system comprises innate and adaptive immunity. Both arms of the immune response function differently and are driven by different populations of cells. In innate immunity, pathogens are recognized through various pattern recognition molecules, such as C-type lectin receptors, toll-like receptors, nod-like receptors, and retinoic acid–inducible gene-I (RIG-I)-like receptors. In addition, a variety of different cells are involved in this type of response, including neutrophils and other types of granulocytes, macrophages, natural killer (NK) cells, innate lymphoid cells, and mast cells. Adaptive immune responses involve specific antigen receptors encoded by rearranged genes, and T cells and B cells play critical roles in these responses.

Macrophages and dendritic cells (DCs), which act as antigen-presenting cells (APCs), link the innate and adaptive immune responses because they can present antigens to T cells in the context of major histocompatibility complex (MHC) class II molecules and stimulate their proliferation and effector functions after being stimulated via pathogen recognition receptors. IL-1b is a crucial cytokine to induce DC or macrophage activation.  Therefore, it has a regulatory signiciance to monitor the effects of chemicals on susceptibility to infection in individuals.


References

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