Inflammation

Inflammation is a fundamental biological response of body tissues to harmful stimuli, including pathogens, damaged cells or irritants. It represents an essential component of the innate immune system and serves as a protective mechanism to eliminate causative agents, remove injured tissue and initiate repair. The response is driven by immune cells, blood vessels and a wide array of molecular mediators. Although crucial for survival, inflammation that is excessive, prolonged or dysregulated contributes to a range of acute and chronic diseases.

Meaning and Historical Context

The term inflammation originates from Middle Latin inflammatio, meaning “a setting on fire”, reflecting its association with heat and redness. Its linguistic roots trace from Old French usage in the fourteenth century. Early medical authors identified the characteristic signs as manifestations resembling burning or irritation in affected tissues.
Inflammation is frequently confused with infection, but the terms describe different processes. Infection refers to the invasion and proliferation of microorganisms, whereas inflammation describes the host’s immunovascular reaction regardless of the underlying cause. Although infections commonly trigger inflammation, numerous non-infective conditions—including atherosclerosis, autoimmune disorders, ischaemia and trauma—also provoke inflammatory responses.

Biological Basis

Inflammation is a coordinated and complex immune response. Tissue-resident cells such as macrophages, dendritic cells, Kupffer cells and mast cells express pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). When these receptors bind their respective molecules, the cells release chemical mediators that initiate local vascular and cellular reactions.
The principal functions of inflammation are:

• eliminating the initial cause of tissue damage;
• removing dead cells and debris;
• activating repair mechanisms.

Too little inflammation may permit uncontrolled microbial growth, while excessive or prolonged inflammation may lead to collateral tissue destruction. Chronic inflammatory reactions underpin various non-communicable diseases including atherosclerosis, osteoarthritis, allergic disorders and periodontal disease.
Type 1 and Type 2 inflammatory responses reflect distinct cytokine environments driven by different T-helper cell subsets (Th1 and Th2), contributing to different patterns of tissue reaction and disease.

Causes of Inflammation

Inflammation arises from diverse stimuli:

• Physical causes such as blunt or penetrating trauma, burns and foreign bodies.
• Biological causes including bacterial, viral, fungal or parasitic infections, as well as immune hypersensitivity reactions.
• Chemical causes including toxins, corrosive agents, alcohol and pollutants.
• Psychological and physiological stress which may indirectly modulate inflammatory pathways.

These triggers activate immune pathways that vary in intensity and duration depending on the nature of the insult.

Acute Inflammation

Acute inflammation is a rapid, short-term process that appears within minutes or hours of injury and subsides once the harmful stimulus is removed. It is characterised by increased movement of plasma and leukocytes, predominantly neutrophils, from the bloodstream into affected tissues. A sequence of vascular and cellular events propagates the reaction.
Typical features of acute inflammation include:

• rapid onset;
• resolution within days;
• involvement of cytokines and chemokines guiding neutrophils and macrophages;
• recognition of pathogens by Toll-like receptors (TLRs);
• common triggers such as allergens, toxins, burns and frostbite.

Subacute inflammation describes processes lasting between two and six weeks, representing a transitional stage between acute and chronic forms.
Acute inflammation ceases when inflammatory mediators degrade or when the initiating stimulus resolves. Because many mediators are short-lived, persistent stimulation is required to maintain the acute phase.

Cardinal Signs

Five classical cardinal signs have long been used to describe inflammation:

• rubor (redness) – caused by vasodilation and increased blood flow;
• calor (heat) – reflecting warm blood from the body’s core reaching the inflamed site;
• tumor (swelling) – due to fluid accumulation and plasma leakage into tissues;
• dolor (pain) – arising from chemical mediators such as histamine and bradykinin stimulating nerve endings;
• functio laesa (loss of function) – thought to reflect pain-mediated reflexes, swelling or impaired tissue capability.

These signs were first documented by Aulus Cornelius Celsus in the first century AD, with later physicians such as Galen contributing to the formulation of loss of function.

Acute Inflammatory Process

At the onset of injury, resident immune cells recognise PAMPs or DAMPs and release mediators that produce the cardinal signs. Vasodilation increases heat and redness, while enhanced vascular permeability produces swelling. Leukocytes migrate through vessel walls via extravasation and follow chemotactic gradients to the injury site, where they engulf pathogens and debris. Plasma protein cascades including the complement, coagulation and fibrinolytic systems operate in parallel to promote pathogen clearance and tissue repair.

Chronic Inflammation

Chronic inflammation develops when an injurious stimulus persists for months or years or when the acute response fails to resolve. It is characterised by infiltration of macrophages, lymphocytes and plasma cells rather than neutrophils. Tissue destruction and repair processes occur simultaneously, often leading to fibrosis.
Chronic inflammation is associated with a wide spectrum of conditions:

• non-communicable diseases such as type 2 diabetes, cardiovascular disease and chronic obstructive pulmonary disease;
• allergic disorders linked to inappropriate immune activation;
• lifestyle factors including obesity, smoking, poor diet and chronic stress.

Vascular Components of Inflammation

Inflammation involves substantial vascular changes. Vasodilation increases blood flow, while enhanced vascular permeability enables plasma proteins and fluid to enter tissue spaces. These processes contribute to oedema and create an environment conducive to leukocyte migration. Endothelial cells play a crucial regulatory role in mediating these changes through expression of adhesion molecules and interaction with circulating immune cells.