Chronic Inflammation: Introduction

Chronic inflammation is a prolonged, persistent immune response lasting weeks, months, or even years. Unlike acute inflammation, which resolves quickly, chronic inflammation persists when the triggering stimulus is difficult to eliminate or when self-antigens drive ongoing immune reactivity. This sustained response distinguishes it from the acute inflammatory response.

Chronic inflammation involves lymphocytes, macrophages, fibroblasts, and connective tissue cells. Unlike acute inflammation dominated by neutrophils, chronic lesions feature mononuclear cell infiltration with less swelling but greater cellular infiltration. These cells work together in ongoing immune activity and tissue repair processes.

Macrophages and other immune cells release enzymes and reactive molecules that damage not only the affected area but also surrounding healthy tissue. Progressive tissue destruction occurs through matrix metalloproteinases, lysosomal enzymes, and reactive oxygen and nitrogen species. This collateral damage is a hallmark of chronic inflammatory conditions.

Fibrosis is the buildup of scar tissue that develops when fibroblasts increase collagen production to contain tissue damage. Although stabilizing the affected area, scar tissue replaces functional parenchyma and reduces organ performance. Fibrogenic signals like TGF-β drive myofibroblast differentiation and collagen cross-linking, increasing tissue stiffness.

A granuloma is a compact, organized structure of activated macrophages surrounded by lymphocytes and connective tissue that helps contain pathogens and foreign material. It forms in some chronic conditions when the inciting agent resists elimination. Granulomas may develop central necrosis, such as caseating necrosis in tuberculosis.

Macrophages sustain chronic inflammation through feedback with T cells. Interferon-γ from Th1 cells drives classical macrophage activation, while macrophage IL-12 induces Th1 cells to produce more interferon-γ. Persistent cytokine and chemokine production maintains leukocyte influx and ongoing immune cell recruitment and activation.

Chronic inflammation shows less swelling and fluid buildup but greater cellular infiltration by mononuclear cells compared to acute inflammation. Morphologically, chronic lesions feature progressive tissue destruction with concurrent healing attempts through angiogenesis and fibrosis. Edema is less prominent while cellular infiltration predominates.