Acute Inflammation



Acute inflammation is the body's rapid response system for infection and damage. It forms part of the innate immune system and has cellular and humoral (chemical) components.

Basic Features

The process of acute inflammation is characterised by four features that are traditionally referred to as the cardinal signs of inflammation and were first described in the First Century AD by Celsus.

Celsus was Roman and it is therefore understandable that he used Latin to describe these features. The medical profession needs little encouragement to incorporate Latin or Greek terms into its technical vocabulary, so for completeness the Latin equivalents are rubor, tumor, calor and dolor respectively.

Around seventeen hundred years later, Virchow added a fifth feature, loss of function (the Latin equivalent laesio functae, somewhat breaks up the rhythm of the first four terms).

These four features are a direct consequence of the pathological events which occur in acute inflammation and that are essential for the acute inflammatory response to take place and function.

Acute inflammation causes increased blood flow to the affected region by dilatation of the blood vessels (vasodilatation). This hyperaemia is responsible for the redness and warmth and serves to increase the delivery of the various elements of the acute inflammatory system to the site of the inflammation.

To facilitate the access of the agents of acute inflammation to the fray further, capillary permeability increases, yielding oedema.

Pain is the result of the release of various substances by the damaged tissue and the inflammatory mediators. Pain encourages the organism to protect the inflamed region and discourages movement, which may be important in some instances of healing. In humans, pain may also prompt the individual to seek medical assistance to resolve the problem.

Cellular Components

Neutrophil Neutrophils are the cells that are considered to be synonymous with acute inflammation and the response to bacteria. They are phagocytic cells which possess granules that contain various destructive substances such as lysozyme, myeloperoxidase and enzymes that allow them to create hydrogen peroxide and oxygen based free radicals which they use to kill the organisms they ingest.

The nucleus of a neutrophil has several lobes.

Neutrophils only have a lifespan of five days at the best of times. When called into the chaos of acute inflammation they may surive exposure to the fray for only a few minutes.

They constitute around 70% of white cells in the blood.

Eosinophil Like neutrophils, eosinophils are derived from myelopoietic cells in the bone marrow. However, whereas neutrophils are infantry that engage in hand to hand combat with infectious organisms, eosinophils are analagous to a form of artillery. They contain numerous red granules that harbour assorted anti-microbial substances which include histamine, eosinophil cationic protein and major basic protein. When called into battle, eosinophils release these substances at their target and are thus adapted to deal with large infectious organisms that are physically too big to be phagocytosed.

Eosinophils are sometimes also thought of as part of the chronic inflammatory response.

Their numbers in the blood are much lower than those of neutrophils and they are typically recruited to deal with specific problems that requires an eosinophilic response, whereas neutrophil involvement is not usually selective.

Mast Cell Mast cells also execute their inflammatory function by discharging the contents of their granules. These granules may not be appreciated with the H+E stain, but can be demonstrated with the chloracetate esterase or toluidine blue stains. The granules contain 5-hydroxytrypatmine and histamine. Degranulation is triggered when multiple IgE molecules are bound to the surface of the mast cell, or if the mast cell is damaged.

Unlike neutrophils, mast cells can live for several years.

In the peripheral blood, they are known as basophils. The basophil count in the blood is normally very low. Basophils and mast cells are of myeloid origin.

Macrophage Macrophages are versatile cells that are also involved in chronic inflammation. In addition to killing organisms by phagocytosis and discharging the contents of granules onto the phagocytosed organisms, they can engulf debris and small foreign particles and present antigens to lymphocytes.

In the blood, macrophages are known as monocytes. They are derived from myeloid cells in the bone marrow. Their nucleus is kidney bean shaped.

Chemical Components

Numerous chemicals are involved in acute inflammation and include multiple cytokines such as assorted interleukins and tumour necrosis factors. However, there are two particular chemical systems which require specific discussion.

Arachidonic Acid

Arachidonic acid is a fatty acid that contains twenty carbon atoms. It is located in cell membranes in combination with the phospholipids of the cell membrane. The expression of the relevant phospholipases by a cell allows arachidonic acid to be cleaved from its place of storage. Other enzymes then convert the arachidonic acid into a variety of metabolites that have assorted effects on smooth muscle and leucocytes, as well as stimulating pain receptors.

Cyclo-oxygenase is the enzyme that begins the conversion of arachidonic acid into its assorted derivatives. It is inhibited by aspirin and other non-steroidal anti-inflammatory drugs (for example, paracetamol) and this enables these drugs to exert their anti-inflammatory and analgesic effects.

Arachidonic Acid Metabolism


Complement is a very old element of the immune system in evolutionary biology that is involved in the response to bacteria. It consists of a cascade of proteins, each of which activates others until finally several components combine to form the membrane attack complex. The membrane attack complex creates a hole in the cell wall of a bacterium, thereby disrupting the osmotic integrity of the organism.

Some components of the complement system also act as signals to white cells and help to co-ordinate the process of acute inflammation.

The presence of complement molecules on the surface of a bacterium makes it easier for phagocytic leucocytes to engulf that organism (opsonisation).

The Cotrol of Acute Inflammation

Acute inflammation begins when either substances on the surface of bacteria or intracellular contents released from damaged cells are detected.

Some bacterial surface components can activate elements of complement and these activated components signal the start of the battle.

Intracellular substances may either be inflammatory mediators in their own right (for example histamine in mast cells) or be exclusively intracellular such that their presence outside a cell can only be interpreted as denoting cell damage that requires an inflammatory response.

Endothelial cells have a vital role in enabling effective acute inflammation to occur. In response to assorted chemicals (for example serotonin) they will contract and thereby render the capillary more permeable. This allows circulating proteins like complement and antibodies to enter the damaged tissue and also assists neutrophil migration from the blood into the tissue. To facilitate neutrophil migration further, the endothelial cells upregulate their synthesis of proteins on their luminal surface that act as anchoring points to which neutrophils can bind. These cell adhesion molecules allow neutrophils to attach to the wall of the capillary (margination), then move into the tissue by extending pseudopodia. The multilobed nucleus of a neutrophils makes it easier for the cell to squeeze through narrow gaps. Tumour necrosis factor alpha is one substance that stimulates this upregulation by endothelial cells.

Relaxation of vascular smooth muscle cells causes vasodilatation, which increases blood flow to the affected tissue and delivers more leucocytes, complement and antibodies. Prostaglandins and histamine are among the substances that promote vasodilatation.

Inflammatory mediators within the tissues provide a chemical signal and gradient for neutrophils to follow. Thus, the process of chemotaxis allows neutrophils to reach the place they are needed by homing in on these beacons (of which complement components C3a and C5a are examples).

Once engaged in battle, neutrophils and macrophages will release other chemicals that enhance the process of chemotaxis and reinforce the pro-inflammatory stance that the endothelial cells have adopted.

Pus is a viscous liquid that is composed of numerous dead neutrophils and bacteria, plus fibrin.

The acute inflammatory response is not only a localised phenomenon. Some interleukins (IL-1 and IL-6) generated by the cells in the inflamed tissues stimulate increased synthesis of neutrophils by the bone marrow. The inflammatory mediators also act on the hypothalamus to resetthe core body temperate to a higher level. This fever is believed to enhance the effectiveness of the immune system while impairing bacterial enzymes. The synthesis of various proteins by the liver is also stimulated.

The acute inflammatory response is self-limiting. Once the infection has been eradicated or the cell damage terminated, the stimuli that drive the inflammation will subside. When this occurs, endothelial cell function returns to normal. Macrophages will then clear up the mess left behind by the bacterial and cellular death and destruction. Other cell types may also need to be called upon to help to restore the inflamed tissue.