Neuroimmunology

Neuroimmunology is a growing branch of biomedical science that studies of all aspects of the interactions between the immune system and nervous system. It deals with, among other things, the physiological functioning of the neuroimmune system in states of both health and disease; malfunctions of the neuroimmune system in disorders (autoimmune diseases, hypersensitivities, immune deficiency), the physical, chemical and physiological characteristics of the components of the neuroimmune system in vitro, in situ, and in vivo.

Background
Neural targets that control thermogenesis, behavior, sleep, and mood can be affected by pro-inflammatory cytokines which are released by activated macrophages and monocytes during infection. Within the central nervous system production of cytokines has been detected as a result of brain injury, during viral and bacterial infections, and in neurodegenerative processes.

From the US National Institute of Health: "Despite the brain's status as an immune privileged site, an extensive bi-directional communication takes place between the nervous and the immune system in both health and disease. Immune cells and neuroimmune molecules such as cytokines, chemokines, and growth factors modulate brain function through multiple signaling pathways throughout the lifespan. Immunological, physiological and psychological stressors engage cytokines and other immune molecules as mediators of interactions with neuroendocrine, neuropeptide, and neurotransmitter systems. For example, brain cytokine levels increase following stress exposure, while treatments designed to alleviate stress reverse this effect.

"Neuroinflammation and neuroimmune activation have been shown to play a role in the etiology of a variety of neurological disorders such stroke, Parkinson's and Alzheimer's disease, multiple sclerosis, pain, and AIDS-associated dementia. However, cytokines and chemokines also modulate CNS function in the absence of overt immunological, physiological, or psychological challenges. For example, cytokines and cytokine receptor inhibitors affect cognitive and emotional processes. Recent evidence suggests that immune molecules modulate brain systems differently across the lifespan. Cytokines and chemokines regulate neurotrophins and other molecules critical to neurodevelopmental processes, and exposure to certain neuroimmune challenges early in life affects brain development. In adults, cytokines and chemokines affect synaptic plasticity and other ongoing neural processes, which may change in aging brains. Finally, interactions of immune molecules with the hypothalamic-pituitary-gonadal system indicate that sex differences are a significant factor determining the impact of neuroimmune influences on brain function and behavior."

History
In 1974 Robert Ader discovered that the immune system of rats can be conditioned to respond to external stimuli unrelated to immune function. Ader was investigating how long conditioned responses (in the sense of Pavlov's conditioning of dogs to drool when they heard a bell ring) might last in laboratory rats. To condition the rats, he used a combination of saccharine-laced water and the drug Cytoxan which induces nausea and suppresses the immune system. Ader was surprised to discover that after conditioning, just feeding the rats saccharine-laced water was sufficient to suppress the immune system of the rats. In other words, a signal via the nervous system (taste) was effecting immune function. This was one of the first scientific experiments that demonstrated that the nervous system can affect the immune system. Ader coined the phrase Psychoneuroimmunology and wrote the two-volume book Psychoneuroimmunology along with David L. Felten and Nicholas Cohen.

In 1981 David Felten, then working at the Indiana University of Medicine, discovered a network of nerves leading to blood vessels as well as cells of the immune system. The researchers also found nerves in the thymus and spleen terminating near clusters of lymphocytes, macrophages and mast cells, all of which help control immune function. This discovery provided one of the first indications of how neuro-immune interaction occurs.