Fatigue in primary Sjögren’s syndrome – A link to sickness behaviour in animals?

Interleukin-1β (IL-1β) is involved in the regulation of sickness behaviour in response to infection and inflammation in animals. Human fatigue can be considered an element of sickness behaviour and is a prominent and often disabling phenomenon in autoimmune diseases such as primary Sjögren’s syndrome (PSS). The role of the IL-1 system in the fatigue of patients with PSS was explored.A cerebrospinal fluid (CSF) analysis of IL-1β, IL-1Ra, and IL-1sRII was performed in 54 PSS patients and 53 control subjects. Fatigue was evaluated in the patients using the Fatigue Severity Scale (FSS) and a fatigue visual analogue scale (VAS); mood was evaluated using the Beck Depression Inventory (BDI).There were higher CSF levels of IL-1Ra pg/mL in PSS patients vs. controls (median 38.4: range 15.4–81.7 vs. 33.7: 7.3–163.1, p = 0.026). Fatigue VAS scores were associated with increasing CSF levels of IL-1Ra in PSS patients (R2 = 0.11, p = 0.015). In a subgroup analysis of the non-depressed PSS patients (N = 37; 69%), the association between VAS scores and IL-1Ra was even stronger (R2 = 0.20, p = 0.006). The positive association between VAS scores and IL-1Ra remained significant in a multiple regression analysis adjusting for age and BDI scores.Increased levels of IL-1Ra in the CSF are associated with increasing fatigue in PSS patients, indicating that the activated IL-1 system is a possible biological factor associated with fatigue.