Fatigue

=== Inflammation ===
Inflammation distorts neural chemistry, brain function and functional connectivity across a broad range of brain networks,<ref>{{cite journal |last1=Korte |first1=S Mechiel |last2=Straub |first2=Rainer H |title=Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms |journal=Rheumatology |date=November 2019 |volume=58 |issue=Suppl 5 |pages=v35–v50 |doi=10.1093/rheumatology/kez413 |pmid=31682277 |pmc=6827268 }}</ref> and has been linked to many types of fatigue.<ref name="pmid31447842"/><ref>{{cite journal |last1=Omdal |first1=Roald |title=The biological basis of chronic fatigue: neuroinflammation and innate immunity |journal=Current Opinion in Neurology |date=June 2020 |volume=33 |issue=3 |pages=391–396 |doi=10.1097/WCO.0000000000000817 |pmid=32304437 |s2cid=215819309 }}</ref> Findings implicate [[neuroinflammation]] in the [[etiology]] of fatigue in [[Autoimmunity|autoimmune]] and related disorders.<ref name="pmid34599320"/><ref name="pmid31447842"/> Low-grade inflammation may cause an imbalance between energy availability and expenditure.<ref>{{cite journal | pmc=5932180 | year=2018 | last1=Lacourt | first1=T. E. | last2=Vichaya | first2=E. G. | last3=Chiu | first3=G. S. | last4=Dantzer | first4=R. | last5=Heijnen | first5=C. J. | title=The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure | journal=Frontiers in Behavioral Neuroscience | volume=12 | page=78 | doi=10.3389/fnbeh.2018.00078 | pmid=29755330 | doi-access=free }}</ref>

[[Cytokines]] are small protein molecules that modulate immune responses and inflammation (as well as other functions) and may have causal roles in fatigue.<ref>{{cite journal | doi=10.3389/fimmu.2017.00021 | doi-access=free | title=Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms | year=2017 | last1=Karshikoff | first1=Bianka | last2=Sundelin | first2=Tina | last3=Lasselin | first3=Julie | journal=Frontiers in Immunology | volume=8 | page=21 | pmid=28163706 | pmc=5247454 }}</ref><ref name="Tarn Evans Traianos et al 2023"/> However a 2019 review was inconclusive as to whether cytokines play any definitive role in [[ME/CFS]].<ref>{{Cite journal|title=A systematic review of cytokines in chronic fatigue syndrome/myalgic encephalomyelitis/systemic exertion intolerance disease (CFS/ME/SEID)|first1=Matthew|last1=Corbitt|first2=Natalie|last2=Eaton-Fitch|first3=Donald|last3=Staines|first4=Hélène|last4=Cabanas|first5=Sonya|last5=Marshall-Gradisnik|date=August 24, 2019|journal=BMC Neurology|volume=19|issue=1|pages=207|doi=10.1186/s12883-019-1433-0|doi-access=free |pmid=31445522|pmc=6708220}}</ref>

The inflammation model may have difficulty in explaining the "unpredictability" and "variability" (i.e. appearing intermittently during the day, and not on all days) of the fatigue associated with inflammatory rheumatic diseases and autoimmune diseases (such as [[multiple sclerosis]]).<ref name="pmid34599320"/>