Acute inflammation resolution involves removing harmful stimuli, clearing debris, and repairing tissue damage. Key processes include cessation of pro-inflammatory mediators, vascular changes, and activation of anti-inflammatory factors like lipoxins and resolvins.

Cellular processes like apoptosis and efferocytosis play crucial roles in resolving inflammation. Impaired resolution can lead to persistent inflammation, tissue damage, fibrosis, and chronic conditions. Understanding these mechanisms is vital for developing targeted therapies.

Resolution of Acute Inflammation

Processes of acute inflammation resolution

• Removal of inflammatory stimuli occurs through immune cells eliminating pathogens (neutrophils, macrophages) and neutralizing harmful substances (antibodies, complement proteins)
• Clearance of cellular debris involves phagocytes engulfing dead cells and tissue fragments while enzymes (matrix metalloproteinases) break down extracellular matrix components
• Cessation of pro-inflammatory mediator production achieved by downregulating cytokine and chemokine synthesis and reducing prostaglandin and leukotriene release
• Vascular changes include decreased permeability and restoration of normal blood flow as endothelial cells repair tight junctions
• Tissue repair initiation begins with activation of fibroblasts to produce collagen and stimulation of angiogenesis for new blood vessel formation

Role of anti-inflammatory mediators

• Lipoxins derived from arachidonic acid inhibit neutrophil recruitment and activation while promoting macrophage efferocytosis of apoptotic cells
• Resolvins from omega-3 fatty acids reduce vascular permeability and enhance macrophage phagocytosis of dying cells
• Protectins decrease pro-inflammatory cytokine production (TNF-α, IL-1β) and promote tissue repair through fibroblast activation
• Maresins stimulate macrophage phenotype switch to M2 anti-inflammatory state and enhance tissue regeneration by promoting stem cell differentiation
• Anti-inflammatory mediators inhibit leukocyte infiltration by downregulating adhesion molecules, promote resolution of edema through increased lymphatic drainage, and stimulate tissue repair processes by activating local stem cells

Cellular Processes and Consequences

Apoptosis and efferocytosis in inflammation

• Apoptosis of activated immune cells prevents excessive tissue damage and reduces release of pro-inflammatory cellular contents (DAMPs)
• Efferocytosis involves macrophages engulfing apoptotic cells preventing secondary necrosis and further inflammation while stimulating release of anti-inflammatory mediators (TGF-β, IL-10)
• Tissue repair promotion occurs as clearance of damaged cells allows for regeneration and efferocytic macrophages release growth factors (VEGF, PDGF)
• Immune response regulation achieved through induction of tolerance to self-antigens presented by apoptotic cells and suppression of adaptive immune responses by regulatory T cells

Consequences of impaired resolution

• Persistent inflammation leads to continued recruitment of inflammatory cells and prolonged release of pro-inflammatory mediators (IL-6, TNF-α)
• Tissue damage results from excessive production of reactive oxygen species and degradation of extracellular matrix components by unchecked proteases
• Fibrosis develops due to excessive deposition of collagen and other matrix proteins impairing organ function (liver cirrhosis, pulmonary fibrosis)
• Chronic inflammatory conditions may arise (rheumatoid arthritis, inflammatory bowel disease, atherosclerosis)
• Systemic effects include increased risk of cardiovascular diseases and metabolic dysregulation (insulin resistance)
• Autoimmune disorders can develop due to loss of self-tolerance and production of autoantibodies against cellular components exposed during prolonged inflammation