A fever is a body temperature that is higher than normal. A normal temperature can vary from person to person, but it is usually around 98.6 F. A fever is not a disease. It is usually a sign that your body is trying to fight an illness or infection.

Infections cause most fevers. You get a fever because your body is trying to kill the virus or bacteria that caused the infection. Most of those bacteria and viruses do well when your body is at your normal temperature. But if you have a fever, it is harder for them to survive. Fever also activates your body's immune system.

Other causes of fevers include

• Medicines, including some antibiotics, blood pressure medicines, and anti-seizure medicines
• Heat illness
• Cancers
• Autoimmune diseases
• Some childhood immunizations

Treatment depends on the cause of your fever. If the fever is very high, your health care provider may recommend taking an over-the-counter medicine such as acetaminophen or ibuprofen. Adults can also take aspirin, but children with fevers should not take aspirin. It is also important to drink enough liquids, to prevent dehydration.

Fever is a system-wide sign of inflammation that raises the body temperature and stimulates the immune response.

A fever is an inflammatory response that extends beyond the site of infection and affects the entire body, resulting in an overall increase in body temperature. Body temperature is normally regulated and maintained by the hypothalamus, an anatomical section of the brain that functions to maintain homeostasis in the body. However, certain bacterial or viral infections can result in the production of pyrogens, chemicals that effectively alter the “thermostat setting” of the hypothalamus to elevate body temperature and cause fever. Pyrogens may be exogenous or endogenous. For example, the endotoxin lipopolysaccharide (LPS), produced by gram-negative bacteria, is an exogenous pyrogen that may induce the leukocytes to release endogenous pyrogens such as interleukin-1 (IL-1), IL-6, interferon-γ (IFN-γ), and tumor necrosis factor (TNF). In a cascading effect, these molecules can then lead to the release of prostaglandin E2 (PGE₂) from other cells, resetting the hypothalamus to initiate fever (Figure).

Like other forms of inflammation, a fever enhances the innate immune defenses by stimulating leukocytes to kill pathogens. The rise in body temperature also may inhibit the growth of many pathogens since human pathogens are mesophiles with optimum growth occurring around 35 °C (95 °F). In addition, some studies suggest that fever may also stimulate release of iron-sequestering compounds from the liver, thereby starving out microbes that rely on iron for growth.

During fever, the skin may appear pale due to vasoconstriction of the blood vessels in the skin, which is mediated by the hypothalamus to divert blood flow away from extremities, minimizing the loss of heat and raising the core temperature. The hypothalamus will also stimulate shivering of muscles, another effective mechanism of generating heat and raising the core temperature.

The crisis phase occurs when the fever breaks. The hypothalamus stimulates vasodilation, resulting in a return of blood flow to the skin and a subsequent release of heat from the body. The hypothalamus also stimulates sweating, which cools the skin as the sweat evaporates.

Although a low-level fever may help an individual overcome an illness, in some instances, this immune response can be too strong, causing tissue and organ damage and, in severe cases, even death. The inflammatory response to bacterial superantigens is one scenario in which a life-threatening fever may develop. Superantigens are bacterial or viral proteins that can cause an excessive activation of T cells from the specific adaptive immune defense, as well as an excessive release of cytokines that overstimulates the inflammatory response. For example, Staphylococcus aureus and Streptococcus pyogenes are capable of producing superantigens that cause toxic shock syndrome and scarlet fever, respectively. Both of these conditions can be associated with very high, life-threatening fevers in excess of 42 °C (108 °F).

A healthy body functions best at an internal temperature of about 37°C (98.6°F). But everyone has their own individual "normal" body temperature, which may be slightly higher or lower. Our bodies also constantly adapt their temperature to environmental conditions. It goes up when we exercise, for instance. And it is lower at night, and higher in the afternoon than in the morning.

Our internal body temperature is regulated by a part of our brain called the hypothalamus. The hypothalamus checks our current temperature and compares it with the normal temperature of about 37°C. If our temperature is too low, the hypothalamus makes sure that the body generates and maintains heat. If, on the other hand, our current body temperature is too high, heat is given off or sweat is produced to cool the skin.

Strictly speaking, body temperature refers to the temperature in the hypothalamus and in the vital internal organs. Because we cannot measure the temperature inside these organs, temperature is taken on parts of the body that are more accessible. But these measurements are always slightly inaccurate.

People get a fever when their brain sets the body temperature higher than normal. This may happen as a reaction to germs such as viruses or bacteria, but it can also happen as a reaction to substances that are made by the body, such as prostaglandins. Our body produces prostaglandins to fight off germs.

A body temperature of 38°C (100.4°F) or more is considered to be a fever. Temperatures above 39.5°C (103.1°F) are considered to be a high fever, and very high fever is defined as any temperature above 41°C (105.8°F). A temperature between 37.5°C and 38°C is an elevated body temperature.

The regulation of body temperature doesn't always work perfectly in younger children. Compared to older children and adults, they also sweat less when it is warm, and it takes longer for them to start sweating. That is why they are more likely to react with a fever. Babies and young children have a higher body temperature than older children. This is because their body surface area is larger in relation to their body weight. Their metabolism is more active too. Newborns usually have an average body temperature of 37.5°C.

The inflammatory response, or inflammation, is triggered by a cascade of chemical mediators and cellular responses that may occur when cells are damaged and stressed or when pathogens successfully breach the physical barriers of the innate immune system. Although inflammation is typically associated with negative consequences of injury or disease, it is a necessary process insofar as it allows for recruitment of the cellular defenses needed to eliminate pathogens, remove damaged and dead cells, and initiate repair mechanisms. Excessive inflammation, however, can result in local tissue damage and, in severe cases, may even become deadly.

Acute Inflammation

An early, if not immediate, response to tissue injury is acute inflammation. Immediately following an injury, vasoconstriction of blood vessels will occur to minimize blood loss. The amount of vasoconstriction is related to the amount of vascular injury, but it is usually brief. Vasoconstriction is followed by vasodilation and increased vascular permeability, as a direct result of the release of histamine from resident mast cells. Increased blood flow and vascular permeability can dilute toxins and bacterial products at the site of injury or infection. They also contribute to the five observable signs associated with the inflammatory response: erythema (redness), edema (swelling), heat, pain, and altered function. Vasodilation and increased vascular permeability are also associated with an influx of phagocytes at the site of injury and/or infection. This can enhance the inflammatory response because phagocytes may release proinflammatory chemicals when they are activated by cellular distress signals released from damaged cells, by PAMPs, or by opsonins on the surface of pathogens. Activation of the complement system can further enhance the inflammatory response through the production of the anaphylatoxin C5a. Figure 17.23 illustrates a typical case of acute inflammation at the site of a skin wound.

Figure 17.23 (a) Mast cells detect injury to nearby cells and release histamine, initiating an inflammatory response. (b) Histamine increases blood flow to the wound site, and increased vascular permeability allows fluid, proteins, phagocytes, and other immune cells to enter infected tissue. These events result in the swelling and reddening of the injured site, and the increased blood flow to the injured site causes it to feel warm. Inflammation is also associated with pain due to these events stimulating nerve pain receptors in the tissue. The interaction of phagocyte PRRs with cellular distress signals and PAMPs and opsonins on the surface of pathogens leads to the release of more proinflammatory chemicals, enhancing the inflammatory response.

During the period of inflammation, the release of bradykinin causes capillaries to remain dilated, flooding tissues with fluids and leading to edema. Increasing numbers of neutrophils are recruited to the area to fight pathogens. As the fight rages on, pus forms from the accumulation of neutrophils, dead cells, tissue fluids, and lymph. Typically, after a few days, macrophages will help to clear out this pus. Eventually, tissue repair can begin in the wounded area.

When acute inflammation is unable to clear an infectious pathogen, chronic inflammation may occur. This often results in an ongoing (and sometimes futile) lower-level battle between the host organism and the pathogen. The wounded area may heal at a superficial level, but pathogens may still be present in deeper tissues, stimulating ongoing inflammation. Additionally, chronic inflammation may be involved in the progression of degenerative neurological diseases such as Alzheimer’s and Parkinson’s, heart disease, and metastatic cancer.

Chronic inflammation may lead to the formation of granulomasa, pockets of infected tissue walled off and surrounded by WBCs. Macrophages and other phagocytes wage an unsuccessful battle to eliminate the pathogens and dead cellular materials within a granuloma. One example of a disease that produces chronic inflammation is tuberculosis, which results in the formation of granulomas in lung tissues. A tubercular granuloma is called a tubercle.

Chronic inflammation is not just associated with bacterial infections. Chronic inflammation can be an important cause of tissue damage from viral infections. The extensive scarring observed with hepatitis C infections and liver cirrhosis is the result of chronic inflammation.