tion with compounds targeting LXR could further modulate lipid rafts and AIRD drug efficacies remains to become explored. In some circumstances, the dose of lipid-modifying therapies should be adjusted once they are employed in mixture with AIRD therapies. Tocilizumab normalizes CYP enzyme expression and increases LDL-C; consequently patients on statin cotherapy may require an improved dose to retain therapeutic lipid-lowering added benefits (135). Cyclosporin may also influence the pharmacokinetics of statins by way of the inhibition of both organic anion transporter 15-LOX Inhibitor Biological Activity polypeptide-1B1 and CYP3A4 (178). Also, lipids including HDL play an important role as S1P chaperones; for that reason, alterations in lipoprotein metabolism could influence the efficacy of drugs modulating the S1P pathway (e.g., fingolimod), that are now applied in several sclerosis and being investigated in AIRDs (34, 179).R E V I E W S E R I E S : I M M U N O M E TA B O L I S 5-HT6 Receptor Agonist Molecular Weight MDietary patterns also modify inflammation; those having a higher inflammatory potential are considerably related with unfavorable lipid profiles in addition to a higher incidence of CVD (180). In spite of these observations, the connection in between nutrition and inflammation in AIRDs just isn’t effectively established. Oral lipid supplements might help the effectiveness of conventional therapies, for example critical fatty acid supplementation to boost STM levels; these have already been linked to decreased joint pain and predict DMARD responsiveness in RA (31). Dietary polyunsaturated fatty acids can also inhibit ferroptosis (181) and incorporate into T cell membranes, therefore altering plasma membrane phospholipid expression and the localization of immunogenic receptors for example IL-2 receptor and Fc receptors into lipid raft microdomains (182). Dietary intervention to alter blood lipids may be helpful in SLE and RA and lessen disease activity scores (18385). Improved dietary intake of omega-3 fatty acids increased HDL and reduced triglycerides in juvenile-onset SLE (183, 186) and elevated HDL and decreased VLDL in adult SLE (187). Hence omega-3 dietary supplements could be promising therapeutic options for some individuals. In contrast, a randomized controlled trial of dietary restrictive patterns decreased weight and fatigue in adults with SLE, but did not impact illness activity or cardiovascular parameters like lipid profiles and inflammatory markers (188).ConclusionUnderstanding how lipid metabolism influences immune responses along with the effect of both conventional and new therapies on lipid metabolism is an ongoing challenge but could identify new ways to target AIRDs. Better control of inflammation employing optimal combinations of immunosuppressive treatments, as shown in inflammatory bowel disease (189), could result in an improved metabolic/ lipid profile in AIRDs. Improved monitoring of pro-/antiinflammatory lipoprotein fractions using a granular lipoprotein taxonomy method and improved CVD threat stratification biomarkers (171, 172), as an alternative to total HDL/LDL levels, could enhance targeted patient management. This is relevant considering that statins don’t completely normalize proinflammatory HDL fractions (160). Such improved monitoring could allow novel combination interventions, like nonspecific dietary intervention with specific lipid lowering and targeted antiinflammatory therapy. Finally, the clinical relevance of metabolic/lipid biomarkers in AIRDs demands to become explored in longterm research to capture the long-term toxicity of combined therapies too