Editing Hypothalamic–pituitary–adrenal axis (section)

==Immune system==

There is bi-directional communication and feedback between the HPA axis and the [[immune system]]. A number of [[cytokines]], such as [[Interleukin 1-alpha|IL-1]], [[Interleukin-6 receptor|IL-6]], [[IL-10 family|IL-10]] and [[Tumor necrosis factor|TNF-alpha]] can activate the HPA axis, although IL-1 is the most potent. The HPA axis in turn modulates the immune response, with high levels of cortisol resulting in a suppression of immune and inflammatory reactions. This helps to protect the organism from a lethal overactivation of the immune system, and minimizes tissue damage from inflammation.<ref name="isbn_9780444530400"/>

In many ways, the [[Central nervous system|CNS]] is "[[immune privilege]]d", but it plays an important role in the immune system and is affected by it in turn. The CNS regulates the immune system through [[neuroendocrine]] pathways, such as the HPA axis. The HPA axis is responsible for modulating [[Inflammation|inflammatory responses]] that occur throughout the body.<ref name="MD">{{cite journal|last1=Marques-Deak|first1=A|last2=Cizza|first2=G|last3=Sternberg|first3=E|title=Brain-immune interactions and disease susceptibility|journal=Molecular Psychiatry|date=February 2005|volume=10|issue=3|pages=239–250|doi=10.1038/sj.mp.4001643|pmid=15685252|s2cid=17978810|doi-access=}}</ref><ref name="Otmishi">{{cite journal|last1=Otmishi|first1=Peyman|last2=Gordon|first2=Josiah|last3=El-Oshar|first3=Seraj|last4=Li|first4=Huafeng|last5=Guardiola|first5=Juan|last6=Saad|first6=Mohamed|last7=Proctor|first7=Mary|last8=Yu|first8=Jerry|title=Neuroimmune Interaction in Inflammatory Diseases|journal=Clinical Medicine: Circulatory, Respiratory, and Pulmonary Medicine|date=2008|volume=2|pages=35–44|pmc=2990232|pmid=21157520|doi=10.4137/ccrpm.s547}}</ref>

During an immune response, [[proinflammatory cytokines]] (e.g. IL-1) are released into the peripheral circulation system and can pass through the [[blood–brain barrier]] where they can interact with the brain and activate the HPA axis.<ref name="Otmishi"/><ref name="Tian">{{cite journal|last1=Tian|first1=Rui|last2=Hou|first2=Gonglin|last3=Li|first3=Dan|last4=Yuan|first4=Ti-Fei|title=A Possible Change Process of Inflammatory Cytokines in the prolonged Chronic Stress and its Ultimate Implications for Health|journal=The Scientific World Journal|date=June 2014|volume=2014|pages=780616|pmc=4065693|doi=10.1155/2014/780616|pmid=24995360|doi-access=free}}</ref><ref name="Hall">{{cite journal|last1=Hall|first1=Jessica|last2=Cruser|first2=desAgnes|last3=Podawiltz|first3=Alan|last4=Mummert|first4=Diana|last5=Jones|first5=Harlan|last6=Mummert|first6=Mark|title=Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis|journal=Dermatology Research and Practice|date=August 2012|volume=2012|pages=403908|doi=10.1155/2012/403908|pmid=22969795|pmc=3437281|doi-access=free}}</ref> Interactions between the [[proinflammatory cytokines]] and the brain can alter the [[metabolic activity]] of [[neurotransmitters]] and cause symptoms such as fatigue, [[Depression (mood)|depression]], and mood changes.<ref name="Otmishi"/><ref name="Tian"/> Deficiencies in the HPA axis may play a role in allergies and inflammatory/ autoimmune diseases, such as [[rheumatoid arthritis]] and [[multiple sclerosis]].<ref name="MD"/><ref name="Otmishi"/><ref name="Bellavance">{{cite journal|last1=Bellavance|first1=Marc-Andre|last2=Rivest|first2=Serge|title=The HPA-immune axis and the immunomodulatory actions of glucocorticoids in the brain|journal=Frontiers in Immunology|date=March 2014|volume=5|pages=136|doi=10.3389/fimmu.2014.00136|pmid=24744759|pmc=3978367|doi-access=free}}</ref>

When the HPA axis is activated by [[stressors]], such as an [[immune response]], high levels of [[glucocorticoids]] are released into the body and suppress immune response by inhibiting the expression of proinflammatory cytokines (e.g. [[Interleukin 1|IL-1]], [[TNF alpha]], and [[IFN gamma]]) and increasing the levels of anti-inflammatory cytokines (e.g. [[Interleukin 4|IL-4]], [[Interleukin 10|IL-10]], and [[Interleukin 13|IL-13]]) in immune cells, such as [[monocytes]] and [[neutrophils]].<ref name="Otmishi"/><ref name="Tian"/><ref name="Bellavance"/><ref name="Padgett">{{cite journal|last1=Padgett|first1=David|last2=Glaser|first2=Ronald|title=How stress influences the immune response|journal=Trends in Immunology|date=August 2003|volume=24|issue=8|pages=444–448|doi=10.1016/S1471-4906(03)00173-X|url=http://www.direct-ms.org/pdf/ImmunologyGeneral/Stress%20and%20immunity.pdf|access-date=12 February 2016|pmid=12909458|archive-url=https://web.archive.org/web/20160327154337/http://www.direct-ms.org/pdf/ImmunologyGeneral/Stress%20and%20immunity.pdf|archive-date=2016-03-27|url-status=dead}}</ref>

The relationship between chronic stress and its concomitant activation of the HPA axis, and dysfunction of the immune system is unclear; studies have found both [[immunosuppression]] and hyperactivation of the immune response.<ref name="Padgett"/>