Powerful anti‐inflammatory action of luteolin: Potential increase with IL‐38

Abstract

Luteolin belongs to the flavone family originally present in some fruits and vegetables, including olives, which decrease intracellular levels of reactive oxygen species (ROS) following the activation of various stimuli. Luteolin inhibits inflammation, a complex process involving immune cells that accumulate at the site of infectious or non-infectious injury, with alteration of the endothelium leading to recruitment of leukocytes. Cytokines have been widely reported to act as immune system mediators, and IL-1 family members evolved to assist in host defense against infections. Interleukin (IL)-1 and Toll-like receptor (TLR) are involved in the innate immunity in almost all living organisms. After being synthesized, IL-1 induces numerous inflammatory mediators including itself, other pro-inflammatory cytokines/chemokines, and arachidonic acid products, which contribute to the pathogenesis of immune diseases. Among the 11 members of the IL-1 family, there are two new cytokines that suppress inflammation, IL-37 and IL-38. IL-38 binds IL-36 receptor (IL-1R6) and inhibits several pro-inflammatory cytokines, including IL-6, through c-Jun N-terminal kinase (JNK) induction and reducing AP1 and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) activity, alleviating inflammatory diseases. Therefore, since luteolin, IL-37 and IL-38 are all anti-inflammatory molecules with different signaling pathways, it is pertinent to recommend the combination of luteolin with these antiinflammatory cytokines in inflammation.

Clinical and Non-clinical Proof of Concept Supporting the Development of RJX As an Adjunct to Standard of Care Against Severe COVID-19

“…IL-1, IL-6, TNF-α, and TGF-β are important pro-inflammatory cytokines that contribute to the pathophysiology of the cytokine release syndrome (CRS), ARDS and multi-organ failure in critically sick adult COVID-19 patients with viral sepsis [13][14][15][16][17][18][19][20][21][22][23] as well as children and adolescents with COVID-19 who develop a multi-system inflammatory syndrome (MIS-C) [59][60][61][62]. Recently, we demonstrated that RJX prevents in the LPS-GalN mouse model of sepsis the marked increase of each of these cytokines in the serum as well as lungs and liver [26].…”

Genetic variation of interleukin-1 receptor type 1 is associated with severity of COVID-19 disease

“…Dear Editor, In this journal, Rossotti and colleagues described the potential therapeutic benefit of the inhibition of interleukin (IL) pathways in COVID-19 disease (1). Members of the IL-1 family are central mediators of the COVID-19 cytokine storm (2). Thus, we aim to explore whether a genetic variation of the IL-1 family is associated with COVID-19.…”

Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study

“…Hence, it would be more practically effective to focus on confirmed clinical and diagnostic applications of seroimmunobiomarkers acquired from laboratory-based results. IL-38 is the latest known member of the IL-1 superfamily (IL-36 sub-family) [210,211]. Functionally, IL-38 is a dose (concentration), microenvironment, and receptor-dependent cytokine, acting as pro-inflammatory and anti-inflammatory factors, although the exact role of IL-38 remains unclear.…”