How important is psychoneuroimmunology?

Psychoneuroimmunology is a recent hybrid science that encompasses immunology, endocrinology, neuroscience, psychiatry and psychology. However, the concept that the brain has a profound effect on the physical, as well as the mental, health is not new. For example, the Roman physician Galen, 1800 years B.P., reported that only 20% of his patients had a major physical basis for their medical symptoms. He also noted that melancholic women were more prone to develop cancer than those with a sanguine temperament. Anecdotal reports occurred in the medical literature regarding the association of different types of cancer with depression. Later, it was observed that the survival time of a patient with a serious, life-threatening infection (such as TB or AIDs) is significantly affected by the psychological state of the patient. The more positive the attitude to the infection, the longer the survival time. Thus, by the late 20th century there were numerous clinical observations suggesting that the brain has a major effect on the immune system, and conversely, the immune system can affect the mental state. The fundamental basis of psychoneuroimmunology was a serious subject of basic research before clinically relevant studies were undertaken. Hans Seyle, in the 1930’s, developed the concept of homeostasis to stress in which he showed that the hypothalamic-pituitary-adrenal (HPA) axis, and the immune system, played an essential role in the adaptive response. Later, investigators in the Soviet Union, the USA and Europe demonstrated that changes in the immune system could be classically conditioned in the Pavlovian sense.1 Thus in rodents, an immune response elicited by an unpleasant (painful or noxious) stimulus, termed the unconditioned stimulus, when paired with a neutral conditioning stimulus (for example, light, sound, scratching the skin of the animal) could be observed at a later occasion when the conditioning stimulus alone was applied. By the 1980’s, it was well-established that specific brain lesions could influence the immune system. For example, lesions of the cortex were associated with a decrease in natural killer cell activity, T-cell proliferation and antibody synthesis, while the newly discovered immunotransmitters, the interleukins, were shown to profoundly influence the HPA axis and brain neurotransmitter function.2 By the late 1990’s, it was evident that there is a constant «cross-talk» between the central and peripheral neurotransmitters, the endocrine and immune systems. Some 30+ cytokines and chemokines had been identified, and cytokine receptors were shown to be widely distributed not only on immune cells but also neurons and accessory cells in the brain (microglia and astrocytes). It is now well-established that: