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Event: 1439

Key Event Title

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

Systemic acute phase response

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
Systemic APR
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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

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term

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
Process Object Action
acute-phase response Acute phase proteins increased

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
Interaction with lung cells leading to atherosclerosis KeyEvent Ulla Vogel (send email) Under development: Not open for comment. Do not cite Under Development

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
mouse Mus musculus High NCBI
human Homo sapiens 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
Male High
Female 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

During acute phase response, the plasma concentration of acute phase proteins (APP) changes in more than 25%. APPs that increase their concentration during APR are called positive APP, while negative APP are decreased during APR 1. In humans, positive APPs include C-reactive protein, serum amyloid A, C3 and C4 complement system, mannose-binding lectin, fibrinogen, fibronectin, ferritin, haptoglobin, hemopexin, among others 1,2. In humans the two major APPs are C-reactive protein (CRP) and serum amyloid A (SAA), whose concentration can increase in more than 1000-fold during acute phase response 1. SAA and CRP have been shown to be correlated in humans 3-5.In mice, the major APP are serum amyloid A, haptoglobin and serum amyloid P6.

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

Systemic acute phase response is assessed by measuring APPs concentrations in blood plasma or serum, most often CRP and SAA. In humans, these proteins are measured by immunoassays detecting single or multiple proteins 4,7-12. In addition, CRP is measured by turbidimetric 13-15 and nephelometric assays 16.

In mice, CRP is not a major APP 6, therefore SAA isoforms are measured using ELISA assays or western blot 17-21.

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help
  • Taxonomic applicability: APR is part of the immune response and is observed in vertebrates6.
  • Life stages applicability: This key event is applicable to all life stages.
  • Sex applicability: This key event is applicable to male and females sexes.


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

1            Gabay, C. & Kushner, I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 340, 448-454, doi:10.1056/NEJM199902113400607 (1999).

2            Mantovani, A. & Garlanda, C. Humoral Innate Immunity and Acute-Phase Proteins. N Engl J Med 388, 439-452, doi:10.1056/NEJMra2206346 (2023).

3            Baumann, R. et al. Human nasal mucosal C-reactive protein responses after inhalation of ultrafine welding fume particles: positive correlation to systemic C-reactive protein responses. Nanotoxicology 12, 1130-1147, doi:10.1080/17435390.2018.1498930 (2018).

4            Monse, C. et al. Concentration-dependent systemic response after inhalation of nano-sized zinc oxide particles in human volunteers. Part Fibre Toxicol 15, 8, doi:10.1186/s12989-018-0246-4 (2018).

5            Ridker, P. M., Hennekens, C. H., Buring, J. E. & Rifai, N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342, 836-843, doi:10.1056/NEJM200003233421202 (2000).

6            Cray, C., Zaias, J. & Altman, N. H. Acute phase response in animals: a review. Comp Med 59, 517-526 (2009).

7            Meier, R. et al. Associations of short-term particle and noise exposures with markers of cardiovascular and respiratory health among highway maintenance workers. Environ Health Perspect 122, 726-732, doi:10.1289/ehp.1307100 (2014).

8            Baumann, R. et al. Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes. J Expo Sci Environ Epidemiol 28, 84-91, doi:10.1038/jes.2016.86 (2018).

9            Adetona, A. M. et al. Impact of Work Task-Related Acute Occupational Smoke Exposures on Select Proinflammatory Immune Parameters in Wildland Firefighters. J Occup Environ Med 59, 679-690, doi:10.1097/JOM.0000000000001053 (2017).

10          Andersen, M. H. G. et al. Health effects of exposure to diesel exhaust in diesel-powered trains. Part Fibre Toxicol 16, 21, doi:10.1186/s12989-019-0306-4 (2019).

11          Walker, E. S. et al. Acute differences in blood lipids and inflammatory biomarkers following controlled exposures to cookstove air pollution in the STOVES study. Int J Environ Health Res 32, 565-578, doi:10.1080/09603123.2020.1785402 (2022).

12          Wyatt, L. H., Devlin, R. B., Rappold, A. G., Case, M. W. & Diaz-Sanchez, D. Low levels of fine particulate matter increase vascular damage and reduce pulmonary function in young healthy adults. Part Fibre Toxicol 17, 58, doi:10.1186/s12989-020-00389-5 (2020).

13          Kim, J. Y., Chen, J. C., Boyce, P. D. & Christiani, D. C. Exposure to welding fumes is associated with acute systemic inflammatory responses. Occup Environ Med 62, 157-163, doi:10.1136/oem.2004.014795 (2005).

14          Barregard, L. et al. Experimental exposure to wood-smoke particles in healthy humans: effects on markers of inflammation, coagulation, and lipid peroxidation. Inhal Toxicol 18, 845-853, doi:10.1080/08958370600685798 (2006).

15          Sikkeland, L. I. B. et al. Systemic and Airway Inflammation after Exposure to Fumes from Military Small Arms. Am J Respir Crit Care Med 197, 1349-1353, doi:10.1164/rccm.201709-1857LE (2018).

16          Brand, P. et al. Relationship between welding fume concentration and systemic inflammation after controlled exposure of human subjects with welding fumes from metal inert gas brazing of zinc-coated materials. J Occup Environ Med 56, 1-5, doi:10.1097/JOM.0000000000000061 (2014).

17          Hadrup, N. et al. Acute phase response and inflammation following pulmonary exposure to low doses of zinc oxide nanoparticles in mice. Nanotoxicology 13, 1275-1292, doi:10.1080/17435390.2019.1654004 (2019).

18          Poulsen, S. S. et al. Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice. PLoS One 12, e0174167, doi:10.1371/journal.pone.0174167 (2017).

19          Gutierrez, C. T. et al. Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in mice. Part Fibre Toxicol 20, 4, doi:10.1186/s12989-023-00514-0 (2023).

20          Christophersen, D. V. et al. Accelerated atherosclerosis caused by serum amyloid A response in lungs of ApoE(-/-) mice. FASEB J 35, e21307, doi:10.1096/fj.202002017R (2021).

21          Halappanavar, S. et al. Pulmonary response to surface-coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: a toxicogenomic study. Environ Mol Mutagen 52, 425-439, doi:10.1002/em.20639 (2011).