350px, Ancher, Michael, "The Sick Girl", 1882, Statens Museum for Kunst Sickness behavior is a coordinated set of adaptive behavioral changes that develop in

ill ILL may refer to: * ''I Love Lucy'', a landmark American television sitcom * Illorsuit Heliport (location identifier: ILL), a heliport in Illorsuit, Greenland * Institut Laue–Langevin, an internationally financed scientific facility * Interlibrar ...

individuals during the course of an

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...

. They usually, but not always, accompany

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

and aid survival. Such illness responses include

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...

, depression,

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...

loss of appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...

, sleepiness, hyperalgesia, reduction in grooming and failure to

concentrate A concentrate is a form of substance that has had the majority of its base component (in the case of a liquid: the solvent) removed. Typically, this will be the removal of water from a solution or suspension, such as the removal of water from ...

. Sickness behavior is a motivational state that reorganizes the organism's priorities to cope with infectious

pathogens In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ger ...

. It has been suggested as relevant to understanding depression, and some aspects of the suffering that occurs in

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

History

Sick animals have long been recognized by farmers as having different behavior. Initially it was thought that this was due to physical weakness that resulted from diverting energy to the body processes needed to fight infection. However, in the 1960s, it was shown that animals produced a blood-carried ''factor X'' that acted upon the brain to cause sickness behavior. In 1987, Benjamin L. Hart brought together a variety of research findings that argued for them being survival adaptations that if prevented would disadvantage an animal's ability to fight infection. In the 1980s, the blood-borne factor was shown to be proinflammatory

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

produced by activated

leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mu ...

in the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

in response to lipopolysaccharides (a cell wall component of

Gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

). These cytokines acted by various humoral and

nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system. A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the ...

routes upon the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...

and other areas of the brain. Further research showed that the brain can also learn to control the various components of sickness behavior independently of immune activation.. In 2015, Shakhar and Shakhar suggested instead that sickness behavior developed primarily because it protected the kin of infected animals from transmissible diseases. According to this theory, termed the Eyam hypothesis, after the English Parish of Eyam, sickness behavior protects the social group of infected individuals by limiting their direct contacts, preventing them from contaminating the environment, and broadcasting their health status.

Kin selection Kin selection is the evolutionary strategy that favours the reproductive success of an organism's relatives, even when at a cost to the organism's own survival and reproduction. Kin altruism can look like altruistic behaviour whose evolution ...

would help promote such behaviors through evolution. In a highly prosocial species like humans, however, sickness behavior may act as a signal to motivate others to help and care for the sick individual.

Advantages

General advantage

Sickness behavior in its different aspects causes an animal to limit its movement; the metabolic energy not expended in activity is diverted to the fever responses, which involves raising body temperature. This also limits an animal's exposure to predators while it is cognitively and physically impaired.

Specific advantages

The individual components of sickness behavior have specific individual advantages. Anorexia limits food ingestion and therefore reduces the availability of

iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in ...

in the gut (and from gut absorption). Iron may aid bacterial reproduction, so its reduction is useful during sickness. Plasma concentrations of iron are lowered for this anti-bacterial reason in fever. Lowered threshold for pain ensures that an animal is attentive that it does not place pressure on injured and inflamed tissues that might disrupt their healing. Reduced grooming is adaptive since it reduces water loss.

Inclusive fitness advantages

According to the ' Eyam hypothesis', sickness behavior, by promoting immobility and social disinterest, limits the direct contacts of individuals with their relatives. By reducing eating and drinking, it limits diarrhea and defecation, reducing environmental contamination. By reducing self-grooming and changing stance, gait and vocalization, it also signals poor health to kin. All in all, sickness behavior reduces the rate of further infection, a trait that is likely propagated by

kin selection Kin selection is the evolutionary strategy that favours the reproductive success of an organism's relatives, even when at a cost to the organism's own survival and reproduction. Kin altruism can look like altruistic behaviour whose evolution ...

Social advantage

Humans helped each other in case of sickness or injury throughout their hunter-gatherer past and afterwards. Convincing others of being badly in need of relief, assistance, and care heightened the chance of survival of the sick individual. High direct costs, such as energy spent on fever and potential harm caused by high body temperatures, and high opportunity costs, as caused by inactivity, social disinterest, and lack of appetite, make sickness behavior a highly costly and therefore credible signal of need.

Immune control

Lipopolysaccharides trigger the

to produce

proinflammatory cytokine An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule (a cytokine) that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include inte ...

s IL-1, IL-6, and tumor necrosis factor (TNF). These peripherally released cytokines act on the brain via a fast transmission pathway involving primary input through the

vagus nerve The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and righ ...

s, and a slow transmission pathway involving cytokines originating from the

choroid plexus The choroid plexus, or plica choroidea, is a plexus of cells that arises from the tela choroidea in each of the ventricles of the brain. Regions of the choroid plexus produce and secrete most of the cerebrospinal fluid (CSF) of the central nerv ...

and

circumventricular organs Circumventricular organs (CVOs) ( circum-: around ; ventricular: of ventricle) are structures in the brain characterized by their extensive and highly permeable capillaries, unlike those in the rest of the brain where there exists a blood� ...

and diffusing into the brain parenchyma by volume transmission. Peripheral cytokines are capable of entering the brain directly but are large lipophilic polypeptide proteins that generally do not easily passively diffuse across the blood-brain barrier. They may also induce the expression of other cytokines in the brain that cause sickness behavior. Acute psychosocial stress enhances the ability of an immune response to trigger both inflammation and behavioral sickness.

Behavioral conditioning

The components of sickness behavior can be learned by conditional association. For example, if a

saccharin Saccharin (''aka'' saccharine, Sodium sacchari) is an artificial sweetener with effectively no nutritional value. It is about 550 times as sweet as sucrose but has a bitter or metallic aftertaste, especially at high concentrations. Saccharin is ...

solution is given with a chemical that triggers a particular aspect of sickness behavior, on later occasions the saccharin solution will trigger it by itself.

Medical conditions

Depression

It has been proposed that

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...

is nearly identical with sickness behavior, raising the possibility that it is a maladaptive manifestation of sickness behavior due to abnormalities in circulating cytokines. Moreover, chronic, but not acute, treatment with antidepressant drugs was found to attenuate sickness behavior symptoms in rodents. The mood effects caused by

interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...

following an immune response have been linked to increased activity within the subgenual anterior cingulate cortex, an area involved in the etiology of depression. PDF:http://mbldownloads.com/0808CNS_BrainRegions.pdf Inflammation-associated mood change can also produce a reduction in the functional connectivity of this part of the brain to the

amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex ver ...

medial prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA4 ...

nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for "nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hyp ...

, and

superior temporal sulcus The superior temporal sulcus (STS) is the sulcus separating the superior temporal gyrus from the middle temporal gyrus in the temporal lobe of the brain. A sulcus (plural sulci) is a deep groove that curves into the largest part of the brain, ...

Cancer side effect

In cancer, both the disease and the

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemother ...

treatment can cause proinflammatory cytokine release which can cause sickness behavior as a

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

References

{{DEFAULTSORT:Sickness Behavior Symptoms Evolutionary biology Cytokines