Inflammation

Inflammation is a complex biological defense response used by body tissues. It is a mechanism of innate immunity, meaning it is a general way the body protects itself. The primary goals of inflammation are to eliminate the cause of cell injury. It also works to clear out damaged cells and tissues. Finally, it helps initiate the process of tissue repair. This response is triggered by many different stimuli. These include physical trauma, pathogens like bacteria, toxins, and allergens. It can also be caused by irritants, overuse, or even autoimmune responses.

Acute inflammation is the body's immediate response to a harmful stimulus. This process usually appears within minutes or hours. It typically lasts only a few days and ceases once the stimulus is removed. If the process lasts between two and six weeks, it is called subacute inflammation. Acute inflammation involves a coordinated mobilization of immune, endocrine, and neurological mediators. It relies on the movement of plasma and leukocytes into the injured area. Specifically, granulocytes like neutrophils play a major role here.

The mechanism of acute inflammation begins with resident immune cells. These include macrophages, dendritic cells, histiocytes, Kupffer cells, and mast cells. These cells possess pattern recognition receptors, or PRRs. These receptors bind to two types of molecules. The first are pathogen-associated molecular patterns, known as PAMPs. These are compounds found in pathogens that are different from host molecules. The second are damage-associated molecular patterns, or DAMPs. These are compounds associated with host-related injury and cell damage.

Once these receptors recognize a PAMP or DAMP, the cells undergo activation. They release inflammatory mediators that cause specific physical changes. First, the vascular phase involves vasodilation, which is the widening of blood vessels. Macrophages and endothelial cells release nitric oxide to help this happen. Mast cells and macrophages also release vasoactive amines like histamine and serotonin. This increased blood flow causes redness, known as rubor, and heat, called calor. The vessels also become more permeable, meaning they become leaky. This allows plasma proteins and fluid to leak into the tissue. This accumulation of fluid is called edema, which causes swelling, or tumor.

As the vascular phase progresses, the cellular phase begins. The increased permeability allows leukocytes to move from the blood into the tissue. This process is called extravasation. Neutrophils move toward the injury by following a chemotactic gradient. This gradient is created by local cells to guide them to the site. Other biochemical systems also help. The complement system can activate to promote opsonization, which marks microbes for destruction. The coagulation system forms a protein mesh to protect the site. This mesh can act like construction scaffolding to aid in later repair.

Historically, the signs of inflammation have been documented for a long time. The first four cardinal signs were described by Celsus around 38 BC. These are rubor (redness), tumor (swelling), calor (heat), and dolor (pain). Pain is caused by chemicals like bradykinin and histamine stimulating nerve endings. The fifth sign is loss of function, or functio laesa. This sign was likely added later by Galen, Thomas Sydenham, or Rudolf Virchow. Loss of function can happen due to pain or severe swelling. For example, bronchitis can cause difficulty breathing.

While acute inflammation is protective, chronic inflammation can be harmful. Chronic inflammation lasts for months or even years. It involves a shift toward different cells, such as mononuclear cells, lymphocytes, and plasma cells. This type of inflammation involves simultaneous destruction and healing of tissue. It is associated with many diseases, including atherosclerosis, osteoarthritis, and diabetes. Factors like obesity, smoking, and stress can promote chronic inflammation. It can also lead to symptoms like fatigue, insomnia, and even mood disorders.