Fig. 2From: Interleukin-1-related activity and hypocretin-1 in cerebrospinal fluid contribute to fatigue in primary Sjögren’s syndromeHypothetical model for fatigue. Danger signals activate astroglia to produce and release S100B that bind to TLR4 and RAGE receptors on microglia. Activated microglia produce IL-1β that bind specific receptors (IL-1R1/IL-1RAcPb) on neurons and induce sickness behavior. There are no specific receptors for IL-6 that can modulate neurons in the same manner as for IL-1β, but higher levels of IL-6 may through stimulation of TNFα synthesis reduce the amount of Hcrt-1 in neurons. Low levels of Hcrt-1 can lead to or modulate fatigue through unknown pathwaysBack to article page