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Event: 986

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increase, Increased susceptibility to infection

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Increase, Increased susceptibility to infection
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
IL-1 inhibition AdverseOutcome Takao Ashikaga (send email) Open for citation & comment EAGMST Under Review

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
Homo sapiens Homo sapiens High NCBI
Mus musculus Mus musculus High NCBI
Rattus norvegicus Rattus norvegicus High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

 Severe combined immunodeficiencies (SCIDs) comprise a group of rare, monogenic diseases that are characterized by an early onset and a profound block in the development of T lymphocytes. Given that adaptive immunity is abrogated, patients with SCID are prone to recurrent infections caused by both non-opportunistic and opportunistic pathogens, leading to early death unless immunity can be restored (reviewed by Fischer et al. (Fischer et al., 2015). Human immunodeficiency virus (HIV) is a retrovirus known to attack the CD4+ T lymphocytes. In individuals with chronic HIV infection not on treatment with antiretroviral agents, as the CD4+ count drops they are vulnerable to a multitude of infections which rarely occur in an immunocompetent host, hence the term opportunistic infections (Justiz Vaillant and Naik, 2021). Various immunosuppressive agents such as corticosteroids, antimetabolites, calcineurin inhibitors, glucocorticoids, antithymocyte globulin, antibodies against IL-2RA or CD28, which all suppress T cell function, increase the incidence of opportunistic infection (reviewed by Tasdogan et al. (Tasdogan et al., 2019).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

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

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

The increased susceptibility to infection caused by IL-1RA or anti-IL-1 antibody has been reported in both humans and mice (De Benedetti et al., 2018; Fleischmann et al., 2003).

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

Increased susceptibility to infection is the significant adverse outcome of drugs and chemicals present in the environment. Therefore, drugs or chemicals that have an effect that can cause immunosuppression must be under regulatory scrutiny.


List of the literature that was cited for this KE description. More help

De Benedetti, F., Gattorno, M., Anton, J., et al. (2018), Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes. N Engl J Med 378: 1908-1919, 10.1056/NEJMoa1706314

Fischer, A., Notarangelo, L.D., Neven, B., et al. (2015), Severe combined immunodeficiencies and related disorders. Nat Rev Dis Primers 1: 15061, 10.1038/nrdp.2015.61

Fleischmann, R.M., Schechtman, J., Bennett, R., et al. (2003), Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. Arthritis Rheum 48: 927-934, 10.1002/art.10870

Justiz Vaillant, A.A., Naik, R. 2021. HIV-1 Associated Opportunistic Infections, StatPearls. StatPearls Publishing

Copyright © 2021, StatPearls Publishing LLC., Treasure Island (FL).

Tasdogan, B.E., Ma, M., Simsek, C., et al. (2019), Update on Immunosuppression in Liver Transplantation. Euroasian J Hepatogastroenterol 9: 96-101, 10.5005/jp-journals-10018-1301