IL-37 is increased in brains of children with autism spectrum disorder and inhibits human microglia stimulated by neurotensin

Tsilioni, Irene; Patel, Arti B.; Pantazopoulos, Harry; Berretta, Sabina; Conti, Pio; Leeman, Susan E.; Theoharides, Theoharis C.

doi:10.1073/pnas.1906817116

Cited by 43 publications

(47 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-37 is elevated in patients with inflammatory diseases, including inflammatory bowel disease, SLE, psoriasis, atherosclerosis, pSS, and RA (Table 2), while reduced levels of IL-37 may be associated with disease severity in asthma, insulin resistance, and allergic rhinitis (Dinarello 2018). IL-37 and IL-18R gene expression was increased in brain samples from children with autism spectrum disorder (ASD) compared to non-ASD controls (Tsilioni et al 2019), suggesting a possible attempt to restrain inflammation.…”

Section: Il-37mentioning

confidence: 99%

IL-1 Superfamily Members and Periodontal Diseases

et al. 2020

View full text Add to dashboard Cite

Periodontitis is a complex, multifactorial chronic disease involving continuous interactions among bacteria, host immune/inflammatory responses, and modifying genetic and environmental factors. More than any other cytokine family, the interleukin (IL)–1 family includes key signaling molecules that trigger and perpetuate periodontal inflammation. Over the years, the IL-1 family expanded to include 11 members of cytokines, some with agonist activity (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ), receptor antagonists (IL-1Ra, IL-36Ra), and 2 anti-inflammatory cytokines (IL-37, IL-38). The IL-1 receptor antagonist (IL-1Ra) has emerged as a pivotal player in the defense against periodontitis. IL-33 primarily induces the production of Th2-associated cytokines but acts as an “alarmin” via stimulation of mast cells. The IL-36 subclass of cytokines may be important in regulating mucosal inflammation and homeostasis. IL-37 suppresses innate and acquired immune responses. IL-38 is the most recent member of the IL-1 superfamily and has anti-inflammatory properties similar to those of IL-37 but through different receptors. However, limited evidence exists regarding the role of IL-37 and IL-38 in periodontitis. Despite the development of IL-1 blocking agents, therapeutic blockade of select IL-1 family members for periodontitis has only been partially investigated in preclinical and clinical research, while the development of IL-37 and IL-38 as novel anti-inflammatory drugs has not been considered adequately. Here, we review the key properties of the IL-1 family members and provide insights into targeting or promoting select cytokines as new therapeutic agents.

show abstract

Section: Il-37mentioning

confidence: 99%

IL-1 Superfamily Members and Periodontal Diseases

et al. 2020

View full text Add to dashboard Cite

show abstract

“…3 Cytokines have been widely reported to act as mediators of the immune system, but also of inflammation. 4 Innate immunity evolved to assist in host defense against infection and includes the IL-1 family, of which IL-1β is the most studied member that binds to the type I cytoplasmatic receptor (IL-1R1), which is homologous to the Toll-like receptors (TLRs). 5 Both IL-1 and TLR are involved in the innate immunity possessed by almost all living organisms, but they can also help the acquired immune system, a property present in only a few advanced species including mammals.…”

Section: Introductionmentioning

confidence: 99%

“…Inflammatory responses are necessary for survival in pathological states, but they could also aggravate diseases and are therefore harmful to the host 3 . Cytokines have been widely reported to act as mediators of the immune system, but also of inflammation 4 . Innate immunity evolved to assist in host defense against infection and includes the IL‐1 family, of which IL‐1β is the most studied member that binds to the type I cytoplasmatic receptor (IL‐1R1), which is homologous to the Toll‐like receptors (TLRs) 5 .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Pathogenetic changes in ME/CFS patients may only occur in the brain, especially the hypothalamus, in which case we will have to await the availability of brain tissue to carry out analysis of the proposed biomarkers, as we recently reported for autism spectrum disorder. 64…”

Section: Discussionmentioning

confidence: 99%

Exosome-associated Mitochondrial DNA is Elevated in Patients with ME/CFS and Stimulates Human Cultured Microglia to Secrete IL-1β

Tsilioni

Natelson

2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease that presents with fatigue, sleep disturbances, malaise and cognitive problems. The pathogenesis of ME/CFS is presently unknown and serum levels of potential biomarkers have been inconsistent. Methods: Exosomes were purified from serum obtained from patients with ME/CFS before and after exercise and their content of mitochondrial DNA (mtDNA) was determined by quantitative PCR. Exosomes from both patients and controls were incubated with cultured human microglia and release of interleukin-1beta (IL-1β) was measured by ELISA.Results: Here we show that serum mtDNA, associated with exosomes, is increased in ME/CFS after exercise. Moreover, exosomes isolated from patients with ME/CFS stimulate significant secretion of IL-1β from cultured human microglia. Conclusion: These results provide evidence for a potential novel pathogenetic factor and target for treatment of ME/CFS.

show abstract

IL-37 is increased in brains of children with autism spectrum disorder and inhibits human microglia stimulated by neurotensin

Cited by 43 publications

References 81 publications

IL-1 Superfamily Members and Periodontal Diseases

IL-1 Superfamily Members and Periodontal Diseases

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

Exosome-associated Mitochondrial DNA is Elevated in Patients with ME/CFS and Stimulates Human Cultured Microglia to Secrete IL-1β

Contact Info

Product

Resources

About