How a local reaction becomes systemic
Local injury generates chemical signals that are carried through the bloodstream. These "messengers" include autacoids (arachidonic acid metabolites), kinins, complement components, prostaglandins, and interferons.
When the inflammatory focus reaches a critical size, tissue breakdown products, mediators, and stress (including pain) disrupt local homeostasis. This serves as a trigger for activating the systemic response:
- The nervous, endocrine, and immune systems are activated.
- Stress mechanisms are triggered.
- Bone marrow function is stimulated.
- The production of specific antibodies and cell-mediated immune responses begins.
As a result, classic systemic signs of inflammation develop: fever, leukocytosis, accelerated ESR, dysproteinemia, and intoxication.
Acute-phase reactants
These are proteins and mediators synthesized by macrophages and hepatocytes. They are nonspecific and appear in any tissue injury, linking local processes to systemic ones.
Main representatives:
- Interleukin-1 (IL-1). Activates polymorphonuclear leukocytes, affects T-lymphocytes at the site, stimulates prostaglandin production by the endothelium, and promotes local hemostasis.
- C-reactive protein (CRP). Rises sharply in the blood, suppresses platelet aggregation, and stimulates the cytolytic activity of natural T-killer cells.
- T-kininogen. A kinin precursor that blocks the activity of $\alpha$-cysteine proteinases.
- Apoferritin. Produced in the liver, it induces leukocytes to produce bactericidal superoxide ions.
Checks and balances: antimediators
To prevent inflammation from destroying the body's own tissues, macrophages release antimediators at all stages. Their task is to prevent the excessive accumulation and action of inflammatory substances.
| Antimediator | Mechanism of action |
|---|---|
| Monoamine oxidase (MAO) | Destroys serotonin and catecholamines |
| Arylsulfatase | Cleaves leukotrienes |
| Histaminase | Oxidizes and deaminates histamine |
| Antioxidants | Inactivate oxygen radicals (ceruloplasmin, peroxidase) |
| Protease inhibitors | Destroy plasmin and complement (heparin, $\alpha_1$-antitrypsin) |
Role of glucocorticoids
Glucocorticoids possess the most potent and multifaceted anti-inflammatory effect, acting simultaneously at three levels:
- Molecular. They stimulate the synthesis of antiphospholipids, which inhibit phospholipase A2. This halts the production of prostaglandins, leukotrienes, and platelet-activating factor.
- Vascular. They constrict microvessels, reducing fluid leakage (exudation) into tissues.
- Cellular. They inhibit cell proliferation, suppress the activity of fibroblasts, phagocytes, T- and B-lymphocytes, and reduce cytokine synthesis.
Intoxication in inflammation
The severity of a patient's condition largely depends on intoxication. It is caused both by the damaging factor itself (e.g., infection) and by the absorption of breakdown products from the focus.
The wider the zone of damage (alteration), the more toxins enter the bloodstream. This suppresses the immune and hematopoietic systems and disrupts homeostasis regulation. In severe conditions (sepsis, diffuse peritonitis, burn disease), massive intoxication deprives inflammation of its protective function.
Briefly: answers to topical questions
What proteins are among the main acute-phase reactants of inflammation?
The main acute-phase reactants of inflammation include nonspecific markers synthesized primarily by hepatocytes and macrophages.
- C-reactive protein is the main protein of the group, an inducer of the classical complement activation pathway.
- Serum amyloid P is a protein with a rapid and short-term response to inflammation.
- Fibrinogen is a blood clotting factor.
- Haptoglobin is a transport protein.
- Ceruloplasmin is a nonspecific marker of inflammation.
- $\alpha_2$-Macroglobulin is a protease inhibitor.
- T-kininogen is a kinin precursor.
- Apoferritin is a protein that induces the production of bactericidal ions.
They also include interleukin-1, $\alpha_1$-glycoprotein, transferrin, and peptidoglycans.
What are the clinical criteria for systemic inflammatory response syndrome (SIRS)?
To diagnose systemic inflammatory response syndrome, at least two of the following criteria must be present.
- Body temperature — fever above 38 °C or hypothermia.
- Tachycardia — heart rate greater than 90 beats per minute.
- Tachypnea — respiratory rate greater than 20 breaths per minute, combined with hypocapnia.
- Leukocyte changes — leukocytosis greater than 12×10⁹/L, leukopenia, or the presence of more than 10% immature forms.
Which pro-inflammatory cytokines trigger the synthesis of acute-phase proteins in the liver?
During prolonged tissue destruction and inflammation, the cytokines IL-1 and IL-6 stimulate the synthesis of SAA in the liver.
SAA is an acute-phase protein and the serum precursor of AA-amyloid.
What changes in blood protein fractions are characteristic of dysproteinemia in acute inflammation?
Dysproteinemia in acute inflammation is manifested by a disruption of the normal ratio of blood protein fractions.
- $\alpha$-Globulins and $\beta$-globulins — their concentration increases, in particular, the level of $\alpha_2$-globulins rises.
- $\gamma$-Globulins — their level increases upon activation of the immune system or chronic progression of the process.
- Acute-phase proteins — an increase in the concentration of C-reactive protein, fibrinogen, ceruloplasmin, and haptoglobin is observed.
- Glycoproteins — the content of seromucoids, sialic acids, and total protein-bound hexoses increases.
Remembering the levels of the anti-inflammatory action of glucocorticoids is helped by the MSC abbreviation: Molecular (phospholipase A2 block), Vascular (microvessel constriction), Cellular (suppression of lymphocytes and fibroblasts).
Class and exam questions
Why is inflammation called a systemic reaction if it begins locally?
Because when the lesion reaches critical dimensions, mediators and breakdown products enter the bloodstream. They activate the nervous, endocrine, and immune systems, causing systemic changes in the body.
What are acute-phase reactants and when do they appear?
These are nonspecific proteins (CRP, IL-1, apoferritin, etc.) synthesized by the liver and macrophages in response to any injury. They are detected in the blood within 4–6 hours.
How does the body protect itself from excessive inflammation?
Through antiamediators secreted by macrophages. For example, histaminase destroys histamine, and antioxidants neutralize free radicals, preventing excessive tissue damage.
How do glucocorticoids stop inflammation at the molecular level?
They stimulate the production of antiphospholipases, which block the enzyme phospholipase A2. Because of this, the synthesis of key mediators—prostaglandins and leukotrienes—ceases.
What else to study on this topic
- Mechanisms of fever and dysproteinemia development in inflammation
- Detailed analysis of the arachidonic acid cascade and autacoid synthesis
- The role of natural T-killers in limiting the inflammatory process
- Changes in the hemostasis system against the background of systemic inflammation
- Pathogenesis of burn and traumatic disease as examples of severe intoxication
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