AA in Rheumatoid Arthritis and Lupus

Inflammation and immune dysregulation are at the center of various diseases, including autoimmune diseases, especially rheumatoid arthritis (RA) and systemic lupus erythematosus (lupus). In general, corticosteroids, disease-modifying drugs, and monoclonal antibodies against IL-6 and TNF-α, JAK inhibitors, and various other immunomodulators are extensively used in the treatment of RA and lupus. It is known that EFA (essential fatty acid) metabolism, especially that of AA, is altered in RA and lupus. It is proposed that metabolism of AA and of other PUFAs may play a role in predicting disease progression, prognosis, and response to treatments offered. For this discussion, a better understanding of the interaction between corticosteroids and EFA metabolism is needed.Corticosterone acts on three classes of PLA₂ (calcium-independent PLA₂ [iPLA₂], secretory PLA₂ [sPLA₂], and cytosolic PLA₂ [cPLA₂]) and COX-2 and LOX to produce radical changes in the plasma and tissue concentrations of anti-inflammatory LXA4, resolvins, protectins, and maresins and pro-inflammatory (PGE2), leukotrienes (LTs), interleukin-1β (IL-1β), and platelet-activating factor (PAF) that modulate the inflammatory process. Studies revealed that corticosteroids inhibit the activities of Δ⁶ and Δ⁵ desaturases and, thus, decrease the formation of ω-6 (GLA, DGLA, AA) and ω-3 (EPA and DHA) that would limit the formation of both pro- and anti-inflammatory eicosanoids. Our previous studies revealed that AA and its metabolite LXA4 have potent anti-inflammatory effects. These results suggest that corticosteroids act at various stages of PUFA metabolism, implying that measurement of plasma levels of LA, ALA, GLA, DGLA, AA, EPA, DHA, LXA4, LTs, and TXs and cytokines may aid in predicting and monitoring the efficacy and potential adverse actions of corticosteroids and immunomodulators.