Community-acquired pneumonia (CAP) is a common respiratory disease in children. This prospective cohort study of 110 children with CAP and 100 healthy children investigated the relationship between the levels of vitamin A, D and E and inflammatory markers, such as tumour necrosis factor (TNF-a), interleukin-1 (IL-1), interleukin-10 (IL-10), neutrophils (NE) and C-reactive protein (CRP), in CAP. The haemoglobin, leukocyte concentration, NE, monocytes and CRP concentration in the CAP group showed significant differences (P < 0.05). The levels of vitamin A, D and E in the CAP group were lower than those in the control group, while the levels of TNF-a and IL-1 were higher than in the control group; the differences were statistically significant (P < 0.05). The IL-10 levels showed no significant differences (P > 0.05). Pearson analysis revealed that the vitamin A, D and E levels were all correlated with the TNF-a, IL-10 and CRP levels (P < 0.05). The vitamin A, D and E levels of the CAP children were lower than those of the healthy children. Thus, the content of fat-soluble vitamins is correlated with the secretion of TNF-a and IL-10. The research provides a new direction for the prevention, diagnosis and treatment of CAP.

Lung cancer, acknowledged as one of the most fatal cancers globally, faces limited treatment options on an international scale. The success of clinical treatment is impeded by challenges such as late diagnosis, restricted treatment alternatives, relapse, and the emergence of drug resistance. This predicament has led to a saturation point in lung cancer treatment, prompting a rapid shift in focus towards the tumor microenvironment (TME) as a pivotal area in cancer research. Within the TME, Interleukin-1 (IL-1) is abundantly present, originating from immune cells, tissue stromal cells, and tumor cells. IL-1\'s induction of pro-inflammatory mediators and chemokines establishes an inflammatory milieu influencing tumor occurrence, development, and the interaction between tumors and the host immune system. Notably, IL-1 expression in the TME exhibits characteristics such as staging, tissue specificity, and functional pluripotency. This comprehensive review aims to delve into the impact of IL-1 on lung cancer, encompassing aspects of occurrence, invasion, metastasis, immunosuppression, and immune surveillance. The ultimate goal is to propose a novel treatment approach, considering the intricate dynamics of IL-1 within the TME.

Gasdermin D (GSDMD)-activated inflammatory cell death (pyroptosis) causes mitochondrial damage, but its underlying mechanism and functional consequences are largely unknown. Here, we show that the N-terminal pore-forming GSDMD fragment (GSDMD-NT) rapidly damaged both inner and outer mitochondrial membranes (OMMs) leading to reduced mitochondrial numbers, mitophagy, ROS, loss of transmembrane potential, attenuated oxidative phosphorylation (OXPHOS), and release of mitochondrial proteins and DNA from the matrix and intermembrane space. Mitochondrial damage occurred as soon as GSDMD was cleaved prior to plasma membrane damage. Mitochondrial damage was independent of the B-cell lymphoma 2 family and depended on GSDMD-NT binding to cardiolipin. Canonical and noncanonical inflammasome activation of mitochondrial damage, pyroptosis, and inflammatory cytokine release were suppressed by genetic ablation of cardiolipin synthase (Crls1) or the scramblase (Plscr3) that transfers cardiolipin to the OMM. Phospholipid scramblase-3 (PLSCR3) deficiency in a tumor compromised pyroptosis-triggered anti-tumor immunity. Thus, mitochondrial damage plays a critical role in pyroptosis.

Bacterial infections can activate and mobilize hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) to the spleen, a process termed extramedullary hematopoiesis (EMH). Recent studies suggest that commensal bacteria regulate not only the host immune system but also hematopoietic homeostasis. However, the impact of gut microbes on hematopoietic pathology remains unclear. Here, we find that systemic single injections of Akkermansia muciniphila (A. m.), a mucin-degrading bacterium, rapidly activate BM myelopoiesis and slow but long-lasting hepato-splenomegaly, characterized by the expansion and differentiation of functional HSPCs, which we term delayed EMH. Mechanistically, delayed EMH triggered by A. m. is mediated entirely by the MYD88/TRIF innate immune signaling pathway, which persistently stimulates splenic myeloid cells to secrete interleukin (IL)-1α, and in turn, activates IL-1 receptor (IL-1R)-expressing splenic HSPCs. Genetic deletion of Toll-like receptor-2 and -4 (TLR2/4) or IL-1α partially diminishes A. m.-induced delayed EMH, while inhibition of both pathways alleviates splenomegaly and EMH. Our results demonstrate that cooperative IL-1R- and TLR-mediated signals regulate commensal bacteria-driven EMH, which might be relevant for certain autoimmune disorders.

Dermal adipocyte lineage cells are highly plastic and can undergo reversible differentiation and dedifferentiation in response to various stimuli. Using single-cell RNA sequencing of developing or wounded mouse skin, we classify dermal fibroblasts (dFBs) into distinct non-adipogenic and adipogenic cell states. Cell differentiation trajectory analyses identify IL-1-NF-κB and WNT-β-catenin as top signaling pathways that positively and negatively associate with adipogenesis, respectively. Upon wounding, activation of adipocyte progenitors and wound-induced adipogenesis are mediated in part by neutrophils through the IL-1R-NF-κB-CREB signaling axis. In contrast, WNT activation, by WNT ligand and/or ablation of Gsk3, inhibits the adipogenic potential of dFBs but promotes lipolysis and dedifferentiation of mature adipocytes, contributing to myofibroblast formation. Finally, sustained WNT activation and inhibition of adipogenesis is seen in human keloids. These data reveal molecular mechanisms underlying the plasticity of dermal adipocyte lineage cells, defining potential therapeutic targets for defective wound healing and scar formation.

Oral squamous cell carcinoma (OSCC) is an extremely common head and neck cancer with a poor 5-year survival rate, especially in cases of metastatic disease. Interleukin (IL)-11 reportedly promotes cell growth and the epithelial-mesenchymal transition process in metastasis. However, the molecular mechanisms of IL-11 in OSCC metastasis are unclear. This study found that IL-11 upregulates matrix metalloproteinase 13 (MMP-13) expression in OSCC via the IL-11 receptor alpha subunit/glycoprotein 130 receptors that activate phosphatidyl-inositol 3-kinase, Ak strain transforming, and activator protein 1 signaling, which subsequently enhance MMP-13-induced tumor metastasis. TIMER2.0 analysis revealed a positive correlation between MMP-13 and IL-11 levels (r = 0.454). Moreover, a strong positive association was observed between higher levels of IL-11 expression in OSCC tissue (p < 0.01), lymph node metastasis (p = 0.0154), and clinical disease stage (p = 0.0337). IL-11 knockdown suppressed the migration of OSCC cells (p < 0.05). The evidence indicates that IL-11 can serve as a new molecular therapeutic target in OSCC metastasis.

BACKGROUND: Systemic autoinflammatory diseases (SAIDs) are hyperinflammatory and immune-dysregulation conditions that present in childhood. This kind of disease is a rare disease with early-onset, severe condition and difficult diagnosis, which seriously affects the growth and development of children. Most children need a genetic diagnosis. However, with the limitation of access to genetic testing and the detection of somatic mutations, the diagnosis of SAIDs remains challenging. IL-1 is one of the important cytokines involved in the pathogenesis of SAIDs. Here we briefly review monogenic SAIDs mediated by aberrant IL-1 production, with the aim to further understand the pathogenesis, clinical manifestations and treatments of IL-1 mediated SAIDs.
METHODS: Literature reviews were performed using \"PubMed\" and \"Web of Science\" by searching for the terms \"autoinflammatory diseases\" and \"IL-1\".
RESULTS: Monogenic SAIDs mediated by IL-1 include MKD, FMF, TRAPS, PAAND, PAPA, CAPS, DIRA, Majeed syndrome, NAIAD, NLRC4-MAS, PFIT, APLAID. Monogenic SAIDs have early onset, various clinical manifestations and difficult diagnosis, so early recognition and early treatment can reduce the complications and enhance the quality of life.
CONCLUSIONS: There are many kinds of IL-1 mediated SAIDs. Pediatricians should be alert to SAIDs in the face of the patients with repeated fever, repeated rash and poor effect of routine treatment. The patients should be carried out with gene testing and treatment in time.

Colitis-associated cancer (CAC) is the colorectal cancer (CRC) subtype that is difficult to treat, and shows high mortality. The consumption of flavonoid-rich fructus aurantii extracts (FAE) has been associated with multiple beneficial effects including anti-inflammatory and anti-cancer properties, but the potential effects on the colitis-associated carcinogenesis have not been thoroughly investigated. Recent clinical data show that, as yet, few agents clearly inhibited CRC development in long-standing inflammatory bowel diseases. Here, we identified that FAE showed significant efficiency to inhibit HT-29 cell proliferation. The potential of FAE in vivo was further evaluated in an AOM/DSS-induced CAC mouse model. Intriguingly, FAE diminished the number of polyps in mice. Furthermore, FAE inhibited CAC by regulating the gene expression of Notch/ NF-κB/IL-1 signaling pathways. Collectively, these results were indicative of FAE has great potential in CAC prevention and treatment.

UNASSIGNED: We aimed to evaluate the efficacy and safety of biologic agents targeting three main cytokines, that is, nerve growth factor (NGF), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α), for osteoarthritis (OA) treatment.
UNASSIGNED: Databases (PubMed, Embase, and Cochrane Library) and ClinicalTrials.gov were systematically searched for randomized placebo-controlled trials (RCTs) of biologic agents from inception to November 15, 2020. The outcomes were the mean change in pain, function scores, and the risk of adverse effects (AEs).
UNASSIGNED: Out of the 28 studies with 29 RCTs (8555 individuals) included, biologic agents were superior to placebo in pain relief (standardized mean difference [SMD] = 0.28, 95% confidence interval [CI] = 0.17-0.38, p < 0.001) and function improvement (SMD = 0.30, 95% CI = 0.18-0.43, p < 0.001). The incidence of any AEs (risk ratio [RR] = 1.09, 95% CI = 1.05-1.14, p < 0.001) and discontinuations due to AEs (RR = 1.39, 95% CI = 1.05-1.83, p = 0.021) were higher following treatment with biologic agents while no significant difference was found in serious AEs. Subgroup analyses showed that NGF inhibitors provided superior pain relief (SMD = 0.36, 95% CI = 0.26-0.47, p < 0.001) and function improvement (SMD = 0.41, 95% CI = 0.30-0.51, p < 0.001), whereas IL-1 inhibitors and TNF-α inhibitors did not. Meanwhile, NGF inhibitors increased the incidence of any AEs (RR = 1.12, 95% CI = 1.07-1.17, p < 0.001) and discontinuations due to AEs (RR = 1.48, 95% CI = 1.07-2.06, p = 0.018). IL-1 inhibitors and TNF-α inhibitors showed no difference in safety compared with placebo.
UNASSIGNED: The efficacy and safety of biologic agents vary by mechanism of action. NGF inhibitors can relieve OA-related pain and improve function but involve safety concerns. IL-1 inhibitors and TNF-α inhibitors are relatively safe options but with limited efficacy.

Schizophrenia is a complex, severe psychiatric disorder with a high heritability that affects approximately 1% of the world\'s population. Numerous schizophrenia-related risk genes have been reported in large-scale studies, but the role of most genetic abnormalities in the pathogenesis of the disease is still obscure. In this study, using whole-exome sequencing, we identified a novel nonsense mutation c.1324C > T in the Interleukin 1 receptor accessory protein (IL1RAP) gene in four affected individuals with schizophrenia of a Chinese family. IL1RAP was found involved in initiating the immune responses and regulating synaptic formation. Considering that schizophrenia has been hypothesized to be neurodevelopment disorder for decades, we further explored the influence of altered expression of IL1RAP gene on neuronal growth, and assessed whether this mutation affects the function of IL1RAP protein in IL-1 signaling pathway. We used lentivirus-mediated shRNA to knockdown the IL1RAP gene expression, which suppressed the axon and dendrites growth of cultured mouse cortical neurons. These defects can be recovered by human IL1RAP wild type construct, but not the R442* mutant construct. Furthermore, this mutant even inhibited neuronal growth and IL-1β-induced JNK phosphorylation when overexpressed in cortical neurons. Although overexpression of this mutant in HePG2 cells did not change IL1RAP protein expression, it partially prohibited the IL-1β-induced nuclear translocation of transcript factor NF-κB, indicating that IL1RAP c.1324C > T is a loss-of-function mutation. Our findings show that IL1RAP plays an important role in early stages of neurodevelopment, and the mutation c.1324C > T may contribute to the pathogenesis of schizophrenia.