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Acute Inflammatory Response

Editor: Dian N. Nasuruddin Updated: 6/8/2024 1:59:03 PM


Inflammation is an essential aspect of the innate defense mechanism of the body against infectious or noninfectious etiologies. This mechanism is nonspecific and immediate.[1] The 5 fundamental signs of inflammation include heat (calor), redness (rubor), swelling (tumor), pain (dolor), and loss of function (functio laesa). Increased blood flow leads to redness and heat while swelling results from fluid accumulation. Pain arises from the release of stimulating chemicals, and loss of function reflects a combination of factors. These signs are evident in acute surface inflammation but may not all be observable in internal acute inflammation, particularly within internal organs.[2]

Inflammation can be categorized into 3 types based on the duration of the response to the injurious cause—acute inflammation, which manifests immediately after injury and typically lasts for a few days; chronic inflammation, which can persist for months or even years if acute inflammation fails to resolve; and subacute inflammation, a transitional phase from acute to chronic lasting from 2 to 6 weeks.[3]

Acute inflammation initiates following a specific injury, triggering the release of soluble mediators such as cytokines, acute phase proteins, and chemokines. These substances promote the migration of neutrophils and macrophages to the inflammation site, representing a crucial component of the innate immune response during acute inflammation.[4] If the acute inflammation does not quickly resolve, it will progress to subacute inflammation. If inflammation persists beyond 6 weeks, it transitions from subacute to chronic, marked by the migration of T lymphocytes and plasma cells to the site of inflammation. Prolonged inflammation without recovery leads to tissue damage and fibrosis.[3] Additional varieties of cells, such as macrophages and monocytes, also contribute to both acute and chronic inflammation.[5] 

Issues of Concern

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Issues of Concern

Acute inflammation is an immediate, adaptive response with limited specificity caused by noxious stimuli, such as infection and tissue damage. This response is beneficial and protects against infectious organisms, including Mycobacterium tuberculosis, protozoa, fungi, and other parasites. However, it can become detrimental if not regulated, such as seen in septic shock.[6] The inflammatory pathway consists of a sequence of events involving inducers, sensors, mediators, and effectors.[7]

The inflammatory process is initiated by inducers, including infectious organisms or noninfectious stimuli such as foreign bodies and signals from damaged tissues or necrotic cells. These inducers activate sensors, which are specialized molecules that stimulate the mediators. Mediators are endogenous chemicals that can induce pain, regulate the inflammatory process, and promote tissue repair. They also activate the effectors, which are the tissues and cells involved in the response.[8] These components work together, leading to various pathways in the inflammatory process depending on the type of stimuli. The ultimate goal of the inflammatory process is to restore homeostasis, regardless of the cause.[6]


The causes or inducers of inflammation can be classified into 2  main groups—exogenous and endogenous inducers.[6]

Exogenous Inducers

Tissues attacked by external sources release signals that induce inflammation. These exogenous inducers can be further subdivided into microbial and nonmicrobial categories.

  • Microbial inducers: Microbial inducers can be divided into 2 classes. The first class is pathogen-associated molecular patterns (PAMPs), which are common to all microorganisms. The second class is virulence factors, which are specific to pathogens. Virulence factors trigger the inflammatory response due to the pathogen's activities. Examples include enzymatic activity produced by helminths and exotoxins produced by bacteria, which are detected by sensors.
  • Nonmicrobial inducers: Nonmicrobial inducers include allergens, toxic compounds, irritants, and foreign bodies that are too large to be digested or that cause phagosomal damage in macrophages. Examples of foreign bodies include silica and asbestos. 

Endogenous Inducers

Dead, damaged, malfunctioning, or stressed tissues release signals that induce inflammation. These inflammatory inducers can be divided into 2 major groups—infectious and noninfectious factors.

Infectious factors include bacteria, viruses, and other microorganisms. Noninfectious factors encompass physical and biological injuries. Physical injuries include frostbite, burns, trauma, foreign bodies, ionizing radiation, and chemical compounds such as glucose, fatty acids, toxins, alcohol, and chemical irritants such as nickel and other trace elements. Biological inducers include signals released by damaged cells and physiological responses to excitement.[9]

Clinical Pathology

The assessment of inflammatory markers is used to detect acute inflammation, potentially indicating a specific disease and assessing treatment response. The most common inflammatory markers are C-reactive protein (CRP), erythrocyte sedimentation rate (ESR or Sed-rate), and procalcitonin (PCT).[4]

CRP is an acute-phase reactant widely used in laboratory testing to assess inflammation.[10] CRP is synthesized in the liver, and its transcription is directly regulated by interleukin-6 (IL-6) and indirectly influenced by IL-1β, tumor necrosis factor α (TNF-α), and other cytokines. Research has indicated its ability to bind to bacteria and tissue membranes, enhancing phagocytosis. In addition, CRP can activate the classical complement pathway. CRP is usually present in plasma at a concentration below 5 mg/L.[11]

Various stimuli, such as infection, major trauma, surgery, and chronic inflammatory conditions, can lead to a significant increase in CRP production. Following these stimuli, CRP concentrations rise within hours, doubling within 5 to 8 hours thereafter. In addition, it is widely acknowledged that mild inflammation and viral infections cause CRP concentrations to elevate within the range of 10 to 40 mg/L. In contrast, active inflammation and bacterial infection result in concentrations of 40 to 200 mg/L. Concentrations exceeding 200 mg/L are typically observed in severe bacterial infections and burns. CRP has a half-life of 19 hours.[12]

CRP is a robust analyte; common laboratory variables such as specimen type, delays in specimen processing, and storage temperature have minimal effects on CRP concentration.[13] However, in inflammatory states, CRP can increase markedly from baseline values to very high concentrations, resulting in falsely low results due to overwhelming antigen excess. This prozone effect may occur in single-antibody nephelometric and turbidimetric laboratory assessment methods.[14]

ESR is a nonspecific marker of acute inflammation associated with various pathologies. The levels of ESR are influenced by factors such as age, gender, pregnancy, anemia, red blood cell dysmorphia, obesity, and fibrinogen deficiency.[15] However, the use of the ESR as a screening test in asymptomatic persons is limited by its low sensitivity and specificity. The ESR measures the distance in millimeters that red blood cells (erythrocytes) settle in a vertical column of anticoagulated blood over 1 hour. The ESR rises within 24 to 48 hours of the onset of inflammation and gradually decreases as the inflammation resolves.[16]

PCT is a 116-amino acid peptide precursor of the hormone calcitonin. Typically, PCT levels are typically less than 0.1 ng/mL in healthy individuals. However, in individuals with inflammation or infections, PCT levels increase in circulation in response to inflammatory cytokines and bacterial endotoxins.[17] PCT levels correlate with the severity of bacterial infections and the probability of a positive blood culture. PCT blood tests can aid in differentiating between sepsis of viral or bacterial origin.[18]

Biochemical and Genetic Pathology

Numerous mediators play a crucial role in initiating the cascade of the acute inflammatory process. The first group of mediators comprises toll-like receptors (TLRs), membrane-spanning proteins found on the surfaces of innate immune system cells such as macrophages and dendritic cells. These single-pass membrane-spanning receptors recognize the PAMPs or can recognize endogenous signals activated during tissue or cell damage known as danger-associated molecular patterns (DAMPs).[9] To date, research has identified more than 10 TLRs. An important example is the CD14 (cluster of differentiation 14), a co-receptor for TLR4, which is on the surface of innate immune system cells preferentially expressed in macrophages, monocytes, and neutrophils. TLR4 recognizes lipopolysaccharide, the major component of the outer membrane of gram-negative bacteria (PAMPs). Then, the transmission of PAMPs and DAMPs is mediated by the adapter protein MyD88 (myeloid differentiation 88) and the TLRs. Subsequently, signaling is transmitted through a specific cascade, leading to the nuclear translocation of transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), activator protein-1 (AP-1), or interferon regulatory factor 3 (IRF3).[19][20]

The second group of mediators consists of arachidonic acid mediators. Arachidonic acid is a phospholipid that constitutes the membrane of the body's cells. When activated by inducers such as infection or tissue damage, the enzyme phospholipase can act on the membrane phospholipids to liberate the arachidonic acid. This component can potentially metabolize into 2 main components through either the cyclooxygenase pathway or the 5-lipooxygenase pathway. The cyclooxygenase pathway forms the prostaglandin (PG) mediators, including prostaglandin D2 (PGD2) and thromboxane (which are the bronchoconstrictive prostaglandins), and the bronchoprotective or inhibitory PGE2 and prostacyclin. On the other hand, the 5-lipooxygenase pathway will form the leukotrienes (LTs). Examples of leukotrienes include LTB4, which is neutrophil adhesive and chemotactic, LTC4, D4, and E4, which are involved in the contraction of smooth muscle bronchioles, vasoconstriction, and edema formation.[21]

The third group of mediators comprises mast cells, which originate from precursors in the bone marrow and are widely distributed in connective tissue. These cells become activated in response to tissue damage, with other immune molecules contributing to the activation of these molecules, including the C3a and C5a of the complement cascade, which lead to the degranulation of human mast cells. Mast cells can also be enhanced by cross-linking their high-affinity receptors for immunoglobulin E (IgE). Upon activation, mast cells secrete various pro-inflammatory molecules such as histamine, TNF, kinins, and leukotrienes. Leukotrienes play a crucial role in the delayed response of acute inflammation triggered by mast cell activation.[22]

The complement system is the fourth group of mediators capable of activating acute inflammation. Complements are a set of proteins that interact with each other to initiate a cascade. Many complements can be activated through various pathways, such as the classical, alternative, or mannose-binding lectin pathways. Among the most important complements in acute inflammation are C3a and C5a, which mediate the anaphylatoxins. C5a is known for its chemotactic effect on neutrophils, while C3b serves as an opsonin for phagocytosis. These complements can further activate the membrane attack complex (MAC), which in turn activates neutrophils, monocytes, and mast cells.[23][24]

The last mediator is the Hageman factor—a component of clotting factors crucial in inflammation. Activation of this factor subsequently triggers the kinin system and the production of bradykinin. Bradykinin, in turn, enhances the permeability of blood vessel walls, allowing for leakage. This leakage results in swelling, which is considered a component of acute inflammation.[25][26]

Other mediators and biomarkers of acute inflammation include reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), cytokines (such as IL-6, TNF-α, and chemokines), the formation of DNA adducts, acute-phase proteins such as CRP, inflammation-related growth factors, transcription factors (such as NF-kB), and major immune cell types. The specific mediators and immune cells involved vary and depend on several factors, such as the type of inducer, the duration of the injury, and multiple genetic loci.[27]

Clinicopathologic Correlations

Cardiovascular Disease and Acute Inflammation

Cardiovascular diseases, including atherosclerosis, are the leading cause of death worldwide. In atherosclerosis, inflammatory mediators play a crucial role, from the initial cell recruitment in plaque development to the eventual rupture of the plaque. Cardiac stress, regardless of its cause, first manifests as inflammation with elevated levels of inflammatory chemokines and cytokines in the affected cardiac tissues. Innate immunity is the most immediate defense mechanism against any cardiac tissue damage. Coronary atherosclerosis is the most common cause of myocardial infarction, resulting in cardiac tissue loss. During myocardial infarction, inflammatory cells migrate to the site of necrotic tissue to clear dead cells and debris as the cardiac cells die and become necrotic. Cell death triggers the acute inflammation process, releasing endogenous signals recognized as danger signals. This activates TLR-mediated pathways, which in turn activate the NF-kB pathway, triggering inflammatory responses. Chemokines then recruit leukocytes to the infarcted areas, and cytokines facilitate the adhesion between leukocytes and endothelial cells. TGF-β and IL-10 promote cardiac repair by suppressing inflammation.[9]

Pancreas and Acute Inflammation

Acute pancreatitis is an inflammatory disease of the pancreas caused by obstruction of the pancreatic duct, gene mutation, or alcoholism. Acute pancreatitis is among the most common causes of hospitalization in the United States. Inflammation in acute pancreatitis occurs by the activation of neutrophils and granulocytes, which secrete inflammatory cytokines. NF-κB, Janus kinase-signal transducer and activator of transcription (JAK-STAT), and mitogen-activated protein kinase (MAPK) pathways play crucial roles in cell activation during pancreatitis.[28]

Liver and Acute Inflammation

The liver is the largest internal organ in the human body, and it responds to infection and injury with inflammation as a protective mechanism. Extensive inflammation can cause hepatocyte injury, metabolic changes, ischemia-reperfusion trauma, and persistent hepatic impairment. Acute liver inflammation can progress to damage the liver parenchyma. If acute hepatitis persists, it can develop into chronic hepatitis. The inducer of liver inflammation involves both noninfectious and infectious pathologies. Infectious agents include the hepatitis B virus (HBV) and hepatitis C virus (HCV), while noninfectious agents include alcoholic or nonalcoholic steatohepatitis, drug-induced hepatitis, and ischemic hepatitis.[9]

Kidney and Acute Inflammation

The most common causes of acute kidney inflammation are infection, ischemia or reperfusion, immune complex formation, and complement dysregulation. The primary promoters of kidney inflammation are the epithelial cells of the renal tubules, which secrete cytokines in response to these inducers. These mediators activate the NF-κB and MAPK pathways.[29]

Intestinal Tract and Acute Inflammation

Acute inflammatory diseases of the intestinal tract can decrease a patient's quality of life worldwide. An excessive inflammatory response to gut microbial flora characterizes polygenic inflammatory bowel disease. Inflammatory bowel diseases include Crohn disease and ulcerative colitis. These two diseases are cytokine-driven. Other causes include noninfectious inflammation of the bowel. The system recognizes microbial agents through Toll-like receptors (TLRs). These PAMPs that bind to the TLRs (mainly TLR4) activate the signaling pathways (NF-kB, MAPK), and this activation leads to the production of cytokines and chemokines to combat the infection.[30]

Clinical Significance

There are 5 cardinal signs of inflammation, namely redness (rubor), heat (calor), swelling (tumor), pain (dolor), and loss of function (functio laesa). The heat sensation is a result of increased blood flow in dilated vessels, which carries heat from the core to the naturally cooler extremities. This increased blood flow also causes redness due to an increase in the number of erythrocytes passing through the injured area. Swelling of the area occurs due to increased permeability and dilation of the blood vessels. Pain results from an increase in the pain mediators, either due to direct damage or resulting from an inflammatory response itself. Loss of function can occur due to restricted mobility caused by edema or pain or from the replacement of cells with scar tissue.[31]



Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clinical and experimental immunology. 2007 Feb:147(2):227-35     [PubMed PMID: 17223962]


Zigterman BGR, Dubois L. [Inflammation and infection: cellular and biochemical processes]. Nederlands tijdschrift voor tandheelkunde. 2022 Mar:129(3):125-129. doi: 10.5177/ntvt.2022.03.21138. Epub     [PubMed PMID: 35258243]


Pahwa R, Goyal A, Jialal I. Chronic Inflammation. StatPearls. 2024 Jan:():     [PubMed PMID: 29630225]


Germolec DR, Shipkowski KA, Frawley RP, Evans E. Markers of Inflammation. Methods in molecular biology (Clifton, N.J.). 2018:1803():57-79. doi: 10.1007/978-1-4939-8549-4_5. Epub     [PubMed PMID: 29882133]


Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq-Yap YH, Hezmee MNM. The crucial roles of inflammatory mediators in inflammation: A review. Veterinary world. 2018 May:11(5):627-635. doi: 10.14202/vetworld.2018.627-635. Epub 2018 May 15     [PubMed PMID: 29915501]


Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008 Jul 24:454(7203):428-35. doi: 10.1038/nature07201. Epub     [PubMed PMID: 18650913]

Level 3 (low-level) evidence


Varela ML, Mogildea M, Moreno I, Lopes A. Acute Inflammation and Metabolism. Inflammation. 2018 Aug:41(4):1115-1127. doi: 10.1007/s10753-018-0739-1. Epub     [PubMed PMID: 29404872]


Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell. 2010 Mar 19:140(6):771-6. doi: 10.1016/j.cell.2010.03.006. Epub     [PubMed PMID: 20303867]

Level 3 (low-level) evidence


Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018 Jan 23:9(6):7204-7218. doi: 10.18632/oncotarget.23208. Epub 2017 Dec 14     [PubMed PMID: 29467962]


Gulhar R, Ashraf MA, Jialal I. Physiology, Acute Phase Reactants. StatPearls. 2024 Jan:():     [PubMed PMID: 30137854]


Nehring SM, Goyal A, Patel BC. C Reactive Protein. StatPearls. 2024 Jan:():     [PubMed PMID: 28722873]


Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Frontiers in immunology. 2018:9():754. doi: 10.3389/fimmu.2018.00754. Epub 2018 Apr 13     [PubMed PMID: 29706967]


Aziz N, Fahey JL, Detels R, Butch AW. Analytical performance of a highly sensitive C-reactive protein-based immunoassay and the effects of laboratory variables on levels of protein in blood. Clinical and diagnostic laboratory immunology. 2003 Jul:10(4):652-7     [PubMed PMID: 12853400]


Roberts WL, Schwarz EL, Ayanian S, Rifai N. Performance characteristics of a point of care C-reactive protein assay. Clinica chimica acta; international journal of clinical chemistry. 2001 Dec:314(1-2):255-9     [PubMed PMID: 11718705]


Tishkowski K, Gupta V. Erythrocyte Sedimentation Rate. StatPearls. 2024 Jan:():     [PubMed PMID: 32491417]


Bray C, Bell LN, Liang H, Haykal R, Kaiksow F, Mazza JJ, Yale SH. Erythrocyte Sedimentation Rate and C-reactive Protein Measurements and Their Relevance in Clinical Medicine. WMJ : official publication of the State Medical Society of Wisconsin. 2016 Dec:115(6):317-21     [PubMed PMID: 29094869]


Davies J. Procalcitonin. Journal of clinical pathology. 2015 Sep:68(9):675-9. doi: 10.1136/jclinpath-2014-202807. Epub 2015 Jun 29     [PubMed PMID: 26124314]


Webb AL, Kramer N, Stead TG, Mangal R, Lebowitz D, Dub L, Rosario J, Tak M, Reddy S, Lee JR, Adams J, Banerjee PR, Wallen M, Ganti L. Serum Procalcitonin Level Is Associated with Positive Blood Cultures, In-hospital Mortality, and Septic Shock in Emergency Department Sepsis Patients. Cureus. 2020 Apr 24:12(4):e7812. doi: 10.7759/cureus.7812. Epub 2020 Apr 24     [PubMed PMID: 32467788]


Brennan JJ, Gilmore TD. Evolutionary Origins of Toll-like Receptor Signaling. Molecular biology and evolution. 2018 Jul 1:35(7):1576-1587. doi: 10.1093/molbev/msy050. Epub     [PubMed PMID: 29590394]


Takeda K, Akira S. Toll-like receptors. Current protocols in immunology. 2015 Apr 1:109():14.12.1-14.12.10. doi: 10.1002/0471142735.im1412s109. Epub 2015 Apr 1     [PubMed PMID: 25845562]


Wenzel SE. Arachidonic acid metabolites: mediators of inflammation in asthma. Pharmacotherapy. 1997 Jan-Feb:17(1 Pt 2):3S-12S     [PubMed PMID: 9017783]


Theoharides TC, Alysandratos KD, Angelidou A, Delivanis DA, Sismanopoulos N, Zhang B, Asadi S, Vasiadi M, Weng Z, Miniati A, Kalogeromitros D. Mast cells and inflammation. Biochimica et biophysica acta. 2012 Jan:1822(1):21-33. doi: 10.1016/j.bbadis.2010.12.014. Epub 2010 Dec 23     [PubMed PMID: 21185371]

Level 3 (low-level) evidence


Haddad A, Wilson AM. Biochemistry, Complement. StatPearls. 2024 Jan:():     [PubMed PMID: 31334949]


Bardhan M, Kaushik R. Physiology, Complement Cascade. StatPearls. 2024 Jan:():     [PubMed PMID: 31855355]


Jukema BN, de Maat S, Maas C. Processing of Factor XII during Inflammatory Reactions. Frontiers in medicine. 2016:3():52     [PubMed PMID: 27867935]


Schmaier AH. The contact activation and kallikrein/kinin systems: pathophysiologic and physiologic activities. Journal of thrombosis and haemostasis : JTH. 2016 Jan:14(1):28-39. doi: 10.1111/jth.13194. Epub 2016 Jan 11     [PubMed PMID: 26565070]


Stone WL, Basit H, Burns B. Pathology, Inflammation. StatPearls. 2024 Jan:():     [PubMed PMID: 30521241]


Manohar M, Verma AK, Venkateshaiah SU, Sanders NL, Mishra A. Pathogenic mechanisms of pancreatitis. World journal of gastrointestinal pharmacology and therapeutics. 2017 Feb 6:8(1):10-25. doi: 10.4292/wjgpt.v8.i1.10. Epub     [PubMed PMID: 28217371]


Poveda J, Sanz AB, Rayego-Mateos S, Ruiz-Ortega M, Carrasco S, Ortiz A, Sanchez-Niño MD. NFκBiz protein downregulation in acute kidney injury: Modulation of inflammation and survival in tubular cells. Biochimica et biophysica acta. 2016 Apr:1862(4):635-646. doi: 10.1016/j.bbadis.2016.01.006. Epub 2016 Jan 8     [PubMed PMID: 26776679]


Strober W, Fuss I, Mannon P. The fundamental basis of inflammatory bowel disease. The Journal of clinical investigation. 2007 Mar:117(3):514-21     [PubMed PMID: 17332878]


Punchard NA, Whelan CJ, Adcock I. The Journal of Inflammation. Journal of inflammation (London, England). 2004 Sep 27:1(1):1     [PubMed PMID: 15813979]