Editing Inflammation (section)

== Systemic effects ==
An [[infectious organism]] can escape the confines of the immediate tissue via the [[circulatory system]] or [[lymphatic system]], where it may spread to other parts of the body. If an organism is not contained by the actions of acute inflammation, it may gain access to the lymphatic system via nearby [[lymph vessel]]s. An infection of the lymph vessels is known as [[lymphangitis]], and infection of a lymph node is known as [[lymphadenitis]]. When lymph nodes cannot destroy all pathogens, the infection spreads further. A pathogen can gain access to the bloodstream through lymphatic drainage into the circulatory system.

When inflammation overwhelms the host, [[systemic inflammatory response syndrome]] is diagnosed. When it is due to infection, the term [[sepsis]] is applied, with the terms [[bacteremia]] being applied specifically for bacterial sepsis and [[viremia]] specifically to viral sepsis. [[Vasodilation]] and organ dysfunction are serious problems associated with widespread infection that may lead to [[septic shock]] and death.<ref>{{Cite book |title=StatPearls |vauthors=Ramanlal R, Gupta V |date=2021 |publisher=StatPearls Publishing |location=Treasure Island (FL) |chapter=Physiology, Vasodilation |pmid=32491494 |access-date=22 September 2021 |chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK557562/ |archive-url=https://web.archive.org/web/20210511162804/https://www.ncbi.nlm.nih.gov/books/NBK557562/ |archive-date=11 May 2021 |url-status=live}}</ref>

=== Acute-phase proteins ===
Inflammation also is characterized by high systemic levels of [[acute-phase protein]]s. In acute inflammation, these proteins prove beneficial; however, in chronic inflammation, they can contribute to [[amyloidosis]].<ref name="robspath" /> These proteins include [[C-reactive protein]], [[serum amyloid A]], and [[serum amyloid P]], which cause a range of systemic effects including:<ref name="robspath" />
{{div col|colwidth=25em}}
* Fever
* Increased [[blood pressure]]
* Decreased [[sweating]]
* [[Malaise]]
* [[Anorexia (symptom)|Loss of appetite]]
* [[Somnolence]]
{{div col end}}

=== Leukocyte numbers ===
Inflammation often affects the numbers of leukocytes present in the body:
* [[Leukocytosis]] is often seen during inflammation induced by infection, where it results in a large increase in the amount of leukocytes in the blood, especially immature cells. Leukocyte numbers usually increase to between 15 000 and 20 000 cells per microliter, but extreme cases can see it approach 100 000 cells per microliter.<ref name="robspath" /> Bacterial infection usually results in an increase of [[neutrophil]]s, creating [[neutrophilia]], whereas diseases such as [[asthma]], [[hay fever]], and parasite infestation result in an increase in [[eosinophil]]s, creating [[eosinophilia]].<ref name="robspath" />
* [[Leukopenia]] can be induced by certain infections and diseases, including viral infection, ''[[Rickettsia]]'' infection, some [[protozoa]], [[tuberculosis]], and some cancers.<ref name="robspath" />

=== Interleukins and obesity ===
With the discovery of [[interleukin]]s (IL), the concept of [[systemic inflammation]] developed. Although the processes involved are identical to tissue inflammation, systemic inflammation is not confined to a particular tissue but involves the [[endothelium]] and other organ systems.

Chronic inflammation is widely observed in [[obesity]].<ref name="ParimisettyDorsemans2016">{{Cite journal |vauthors=Parimisetty A, Dorsemans AC, Awada R, Ravanan P, Diotel N, Lefebvre d'Hellencourt C |date=March 2016 |title=Secret talk between adipose tissue and central nervous system via secreted factors-an emerging frontier in the neurodegenerative research |journal=Journal of Neuroinflammation |type=Review |volume=13 |issue=1 |pages=67 |doi=10.1186/s12974-016-0530-x |pmc=4806498 |pmid=27012931 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Kershaw EE, Flier JS |date=June 2004 |title=Adipose tissue as an endocrine organ |journal=The Journal of Clinical Endocrinology and Metabolism |volume=89 |issue=6 |pages=2548–56 |doi=10.1210/jc.2004-0395 |pmid=15181022 |doi-access=free}}</ref> Obese people commonly have many elevated markers of inflammation, including:<ref>{{Cite journal |vauthors=Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M, Vidal H, Hainque B |date=September 2000 |title=Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss |journal=The Journal of Clinical Endocrinology and Metabolism |volume=85 |issue=9 |pages=3338–42 |doi=10.1210/jcem.85.9.6839 |pmid=10999830 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Mohamed-Ali V, Flower L, Sethi J, Hotamisligil G, Gray R, Humphries SE, York DA, Pinkney J |date=December 2001 |title=beta-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies |journal=The Journal of Clinical Endocrinology and Metabolism |volume=86 |issue=12 |pages=5864–9 |doi=10.1210/jcem.86.12.8104 |pmid=11739453 |s2cid=73100391 |doi-access=free}}</ref>
* [[Interleukin-6|IL-6 (Interleukin-6)]]<ref name="Loffreda S 1998">{{Cite journal |vauthors=Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, Diehl AM |date=January 1998 |title=Leptin regulates proinflammatory immune responses |journal=FASEB Journal |volume=12 |issue=1 |pages=57–65 |doi=10.1096/fasebj.12.1.57 |pmid=9438411 |doi-access=free}}</ref><ref name="Esposito K 2002">{{Cite journal |vauthors=Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D |date=October 2002 |title=Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress |journal=Circulation |volume=106 |issue=16 |pages=2067–72 |doi=10.1161/01.CIR.0000034509.14906.AE |pmid=12379575 |doi-access=free}}</ref>

{{columns-list|colwidth=30em|
* [[Interleukin-8|IL-8 (Interleukin-8)]]
* [[Interleukin-18|IL-18 (Interleukin-18)]]<ref name="Loffreda S 1998" /><ref name="Esposito K 2002" />
* [[Tumor necrosis factor-alpha|TNF-α (Tumor necrosis factor-alpha)]]<ref name="Loffreda S 1998" /><ref name="Esposito K 2002" />
* [[C-reactive protein|CRP (C-reactive protein)]]<ref name="Loffreda S 1998" /><ref name="Esposito K 2002" />
* [[Insulin]]<ref name="Loffreda S 1998" /><ref name="Esposito K 2002" />
* [[Blood sugar|Blood glucose]]<ref name="Loffreda S 1998" /><ref name="Esposito K 2002" />
* [[Leptin]]<ref name="Loffreda S 1998" /><ref name="Esposito K 2002" />
}}

Low-grade chronic inflammation is characterized by a two- to threefold increase in the systemic concentrations of cytokines such as TNF-α, IL-6, and CRP.<ref>{{Cite journal |vauthors=Petersen AM, Pedersen BK |date=April 2005 |title=The anti-inflammatory effect of exercise |journal=Journal of Applied Physiology |volume=98 |issue=4 |pages=1154–62 |doi=10.1152/japplphysiol.00164.2004 |pmid=15772055 |s2cid=4776835}}</ref> Waist circumference correlates significantly with systemic inflammatory response.<ref>{{Cite journal |vauthors=Rogowski O, Shapira I, Bassat OK, Chundadze T, Finn T, Berliner S, Steinvil A |date=July 2010 |title=Waist circumference as the predominant contributor to the micro-inflammatory response in the metabolic syndrome: a cross sectional study |journal=Journal of Inflammation |volume=7 |pages=35 |doi=10.1186/1476-9255-7-35 |pmc=2919526 |pmid=20659330 |doi-access=free}}</ref>

Loss of [[white adipose tissue]] reduces levels of inflammation markers.<ref name="ParimisettyDorsemans2016" /> As of 2017 the association of systemic inflammation with [[insulin resistance]] and [[type 2 diabetes]], and with [[atherosclerosis]] was under preliminary research, although rigorous [[clinical trial]]s had not been conducted to confirm such relationships.<ref name="Goldfine">{{Cite journal |vauthors=Goldfine AB, Shoelson SE |date=January 2017 |title=Therapeutic approaches targeting inflammation for diabetes and associated cardiovascular risk |journal=The Journal of Clinical Investigation |volume=127 |issue=1 |pages=83–93 |doi=10.1172/jci88884 |pmc=5199685 |pmid=28045401 |doi-access=free}}</ref>

[[C-reactive protein]] (CRP) is generated at a higher level in obese people, and may increase the risk for [[cardiovascular diseases]].<ref name="Choi">{{Cite journal |vauthors=Choi J, Joseph L, Pilote L |date=March 2013 |title=Obesity and C-reactive protein in various populations: a systematic review and meta-analysis |journal=Obesity Reviews |volume=14 |issue=3 |pages=232–44 |doi=10.1111/obr.12003 |pmid=23171381 |s2cid=206227739}}</ref>