How a Local Reaction Becomes Systemic
Local injury generates chemical signals that are distributed via 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 triggers the systemic response:
- The nervous, endocrine, and immune systems are activated.
- Stress mechanisms are engaged.
- Bone marrow activity is stimulated.
- Specific antibody production and cell-mediated immune reactions begin.
As a result, the classic systemic signs of inflammation develop: fever, leukocytosis, elevated ESR, dysproteinemia, and intoxication.
Acute-Phase Reactants
These are proteins and mediators synthesized by macrophages and hepatocytes. They are nonspecific, appear in response to any tissue injury, and bridge local processes with systemic ones.
Key representatives:
- Interleukin-1 (IL-1). Activates polymorphonuclear leukocytes, affects T lymphocytes at the site of injury, stimulates prostaglandin production by the endothelium, and promotes local hemostasis.
- C-Reactive Protein (CRP). Sharp increases occur in the blood; it suppresses platelet aggregation and stimulates the cytolytic activity of natural killer (NK) cells.
- T-kininogen. A precursor of kinins that blocks the activity of $\alpha$-cysteine proteinases.
- Apoferritin. Formed in the liver, it induces leukocytes to produce bactericidal superoxide ions.
The Check and Balance System: Anti-Mediators
To prevent inflammation from destroying host tissues, macrophages secrete anti-mediators at all stages. Their role is to prevent the excessive accumulation and action of inflammatory substances.
| Anti-Mediator | Mechanism of Action |
|---|---|
| Monoamine Oxidase (MAO) | Degrades 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) |
The Role of Glucocorticoids
Glucocorticoids possess the most potent and multifaceted anti-inflammatory effects, acting at three distinct levels:
- Molecular. They stimulate the synthesis of antiphospholipases, which inhibit phospholipase A2. This halts the production of prostaglandins, leukotrienes, and platelet-activating factor.
- Vascular. They constrict microvessels, reducing fluid exudation into tissues.
- Cellular. They inhibit cell proliferation and suppress the activity of fibroblasts, phagocytes, T and B lymphocytes, as well as reduce cytokine synthesis.
Intoxication in Inflammation
The severity of a patient's condition largely depends on intoxication. This is driven both by the damaging factor itself (such as infection) and by the absorption of breakdown products from the focus.
The broader the zone of alteration (injury), the more toxins enter the bloodstream. This suppresses the immune and hematopoietic systems and disrupts homeostatic regulation. In severe conditions (e.g., sepsis, diffuse peritonitis, burn disease), massive intoxication strips inflammation of its protective function.