General Changes in the Focus of Inflammation
The transition of the inflammatory reaction into its final phase is accompanied by a noticeable decrease in the acuteness of local processes. Vascular congestion (hyperemia) diminishes, exudation intensity drops, and active emigration of blood cells—primarily neutrophils—ceases. At the cellular level, metabolism shifts: catabolic reactions give way to the predominance of anabolic processes.
The main task of this stage is to clear the damaged area of bacterial agents and necrotic debris. To achieve this, monocytes, histiocytes, and macrophages dramatically increase their synthesis of intracellular enzymes (lysosomal hydrolases). Polymorphonuclear leukocytes, having completed their digestive function, undergo mass apoptosis and death.
In aseptic inflammation, where only altered autologous antigens are present, leukocytes leave the focus 18–24 hours later. Only after their departure is the space populated by macrophages, allowing the latter to avoid destructive lysis caused by neutrophil hydrolases.
Formation of the Inflammatory Infiltrate
Gradually, the cellular landscape shifts: dead neutrophils are replaced by mononuclear cells and repair-associated cells, forming a new inflammatory infiltrate.
Its composition includes:
- Hematogenous macrophages and monocytes.
- Immune system cells (T- and B-lymphocytes, plasma cells).
- Platelets.
- Fibroblasts.
Infiltrate cells act as healing regulators. They secrete interleukins (IL), which trigger fibroblast proliferation. Concurrently with the endothelium, neoangiogenesis—the formation of new blood vessels—is activated. Synthesized inflammatory mediators and growth factors stimulate DNA production, initiating regeneration or fibrosis.
Key feature: If immunoglobulins (Igs) accumulate in cell cytoplasm, intercellular space, or vascular walls, this can lead to the formation of granulomas.
Regulation of Proliferation
Cell multiplication relies on a complex control mechanism. Local processes within the lesion serve as a signal to engage systemic mechanisms, transforming local changes into a systemic body-wide response.
Proliferation Activators:
- Anti-inflammatory mediators: glucocorticoids, antioxidants, and hydrolase inhibitors.
- Growth factors: fibroblast, epidermal, nerve, and insulin-like growth factor.
- Cytokines: IL-1 and IL-2 through IL-7.
Proliferation Inhibitors:
- Tumor necrosis factor (TNF).
- Chalones.
Humoral and hormonal regulation play a massive role. Somatotropin, thyroxine, and insulin exert a direct stimulatory effect. Furthermore, regeneration processes are significantly enhanced under the influence of endogenous opiates.
Healing Dynamics and Outcomes
As the cells of the inflammatory infiltrate break down, fibroblasts—originating from local cambial elements—become dominant. Active fibrillogenesis begins: cells synthesize RNA, DNA, and ground substance, gradually transforming into fibrocytes.
The damaged zone is filled with granulation tissue. As described by M.N. Nikiforov (1895), it possesses high resorptive capacity and builds a reliable barrier against pathogens.
The process concludes with the maturation of granulation tissue and the formation of mature connective tissue. There are two possible outcomes:
- Substitution (incomplete regeneration). Most characteristic of inflammation. Granulation tissue matures into a connective tissue scar, the mass of which depends on the depth of the injury.
- Restitution (complete regeneration). Restoration of the original tissue, including all its specific structures and features.