Growing knowledge about the cytokine network response has led to a better comprehension of mechanisms of pathologies and to the development of new treatments with biological drugs, able to block specific molecules of the immune response. Indeed, when the cytokine production is deregulated, diseases often occur. The understanding of the physiological mechanism of the cytokine network would be useful to better comprehend pathological conditions. Moreover, since the immune system and response change their properties with development, differences in patients' age should be taken into account, both in physiological and in pathological conditions. In this study, we analyzed the profile of 48 cytokines and chemokines in the serum of healthy subjects, comparing adults (≥18 years) with young children and children (1–6 and 7–17 years). We found that a certain number of cytokines were not being produced in healthy subjects; others showed a constant serum level amongst the groups. Certain cytokines exhibited a downward or an upward trend with increasing age. The remaining cytokines were up- or downregulated in the group of the children with respect to the other groups. In conclusion, we drew some kinds of guidelines about the physiological production of cytokines and chemokines, underling the difference caused by aging.
Microbial nucleic acid recognition serves as the major stimulus to an antiviral response, implying a requirement to limit the misrepresentation of self nucleic acids as non-self and the induction of autoinflammation. By systematic screening using a panel of interferon-stimulated genes we identify two siblings and a singleton variably demonstrating severe neonatal anemia, membranoproliferative glomerulonephritis, liver fibrosis, deforming arthropathy and increased anti-DNA antibodies. In both families we identify biallelic mutations in DNASE2, associated with a loss of DNase II endonuclease activity. We record increased interferon alpha protein levels using digital ELISA, enhanced interferon signaling by RNA-Seq analysis and constitutive upregulation of phosphorylated STAT1 and STAT3 in patient lymphocytes and monocytes. A hematological disease transcriptomic signature and increased numbers of erythroblasts are recorded in patient peripheral blood, suggesting that interferon might have a particular effect on hematopoiesis. These data define a type I interferonopathy due to DNase II deficiency in humans.
Mevalonate kinase deficiency (MKD) is a rare disorder characterized by recurrent inflammatory episodes and, in most severe cases, by psychomotor delay. Defective synthesis of isoprenoids has been associated with the inflammatory phenotype in these patients, but the molecular mechanisms involved are still poorly understood, and, so far, no specific therapy is available for this disorder. Drugs like aminobisphosphonates, which inhibit the mevalonate pathway causing a relative defect in isoprenoids synthesis, have been also associated to an inflammatory phenotype. Recent data asserted that cell inflammation could be reversed by the addition of some isoprenoids, such as geranylgeraniol and farnesyl pyrophosphate. In this study, a mouse model for typical MKD inflammatory episode was obtained treating BALB/c mice with aminobisphosphonate alendronate and bacterial muramyldipeptide. The effect of exogenous isoprenoids-geraniol, farnesol, and geranylgeraniol-was therefore evaluated in this model. All these compounds were effective in preventing the inflammation induced by alendronate-muramyldipeptide, suggesting a possible role for these compounds in the treatment of MKD in humans. (Pediatr Res 64: 177-182, 2008)
Curcumin belongs to the family of natural compounds collectively called curcuminoids and it possesses remarkable beneficial anti-oxidant, anti-inflammatory, anti-cancer, and neuroprotective properties. Moreover it is commonly assumed that curcumin has also been suggested as a remedy for digestive diseases such as inflammatory bowel diseases (IBD), a chronic immune disorder affecting the gastrointestinal tract and that can be divided in two major subgroups: Crohn's disease (CD) and Ulcerative Colitis (UC), depending mainly on the intestine tract affected by the inflammatory events. The chronic and intermittent nature of IBD imposes, where applicable, long-term treatments conducted in most of the cases combining different types of drugs. In more severe cases and where there has been no good response to the drugs, a surgery therapy is carried out. Currently, IBD-pharmacological treatments are generally not curative and often present serious side effects; for this reason, being known the relationship between nutrition and IBD, it is worthy of interesting the study and the development of new dietary strategy. The curcumin principal mechanism is the suppression of IBD inflammatory compounds (NF-κB) modulating immune response. This review summarizes literature data of curcumin as OPEN ACCESSMolecules 2014, 19 21128 anti-inflammatory and anti-oxidant in IBD, trying to understand the different effects in CD e UC.
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