Search Results (6)

Chronic obstructive pulmonary disease (COPD) is a chronic, debilitating condition that affects the lungs and airways. It is characterized by persistent bronchitis, a condition exemplified by the inflammation of the bronchial tubes, the hypersecretion of mucus, emphysema, and the destruction of the airway parenchyma. The combination of these conditions leads to persistent tissue damage, pulmonary fibrosis, and ongoing inflammation of the airways. The inflammatory response in COPD is a complex process that is orchestrated by a wide range of immune cells. These include lung epithelial cells, monocytes, macrophages, neutrophils, eosinophils, and T and B lymphocytes, among others. These cells work together to produce a wide range of inflammatory biomarkers that are involved in the pathogenesis of COPD. Some of the key inflammatory biomarkers that have been identified in COPD include a variety of cytokines, the C-reactive protein/serum albumin ratio, fibrinogen, soluble receptor for advanced glycation endproducts, club/clara cells in the lungs with a molecular weight of 16 kDa, surfactant protein D, adiponectin, reactive oxygen species, and proteases. This review aims to provide a comprehensive overview of the role of immune cells and key inflammatory biomarkers in the development and progression of COPD. It will delve into the intricacies of the inflammatory response in COPD, exploring the various cell types and biomarkers that are involved in this process. By understanding the underlying mechanisms that drive COPD, we can better develop targeted treatments that can help to alleviate the symptoms of COPD. Full article

VEXAS syndrome is a new disease entity with symptoms that can mimic hematological, rheumatic and dermatological diseases. It is important to take a multidisciplinary approach to patient care, taking into account genetic testing, in which the presence of mutations in the UBA1 gene can confirm the diagnosis. UBA1 mutation has been shown to be involved in the induction of the inflammatory response through many different mechanisms. NF-κB and TNF-α pathways appear to be the most important in VEXAS syndrome. There are many different UBA1 mutations which can result in different outcomes, suggesting it is a possible prognostic factor. Furthermore, mutations differ in how they impair UBA1 function. Cytokines have been shown to be significantly altered in VEXAS patients; however, their exact expression and importance were not clearly defined. Interleukins, such as interleukin (IL)-6, IL-1, IL-2R and others, were reported to be expressed at an altered level, similarly to other cytokines, such as IFN-γ or TNF-α. It is worth noting that the expression of certain cytokines can vary between patients, which poses therapeutic difficulties in selecting the right drug. Therefore, the aim of this review was to describe the cytokines involved in VEXAS syndrome and associate their expression with UBA1 mutation. Full article

Macrophages are myeloid phagocytic leukocytes whose functions are to protect against infections, mediate T-cell responses, and maintain tissue homeostasis. IL-12p40 monomer is a cytokine that is largely produced by macrophages, and it has, for the longest time, been considered a largely non-functional cytokine of the IL-12 family. However, new research has emerged that demonstrates that this p40 monomer may play a bigger role in shaping immune environments. To shed light on the specific effects of p40 monomer on macrophages and their surrounding environment, we showed, through cell culture studies, qPCR, ELISA, and immunofluorescence analyses, that the direct administration of recombinant p40 monomer to RAW 264.7 cells and primary lung macrophages stimulated the production of both pro-inflammatory (TNFα) and anti-inflammatory (IL-10) signals. Accordingly, p40 monomer prevented the full pro-inflammatory effects of LPS, and the neutralization of p40 monomer by mAb a3-3a stimulated the pro-inflammatory effects of LPS. Furthermore, we demonstrated that the intranasal administration of p40 monomer upregulated TNFα⁺IL-10⁺ macrophages in vivo in the lungs of mice. Collectively, these results indicate an important immunoregulatory function of p40 monomer in the upregulation of both pro- and anti-inflammatory molecules in macrophages. Full article

Interceding nutrients have been acquiring increased attention and prominence in the field of healing and deterrence of various disorders. In this light, the present article encompasses several facets of ketogenic diet as an immunomodulator with respect to its expansive clinical applications. Accordingly, several scientific records, models, and case histories, including viral infections, cancer, chronic diseases, e.g., cardiovascular diseases, epilepsy, as well as numerous other neuro-disorders, are assembled, revealing a profound influence of KD in favor of improvement in the patient’s condition. We accentuate possible manifold mechanisms of KD that require further exploration. Full article

Under pathological conditions such as multiple sclerosis (MS), leukocytes infiltrate the central nervous system where they, in concert with activated microglia, promote inflammatory demyelination resulting in a broad spectrum of symptoms, including paralysis. Therefore, all current therapeutic approaches to MS target the immune system, blocking inflammation and paralysis progression, but may compromise the immune system. In this focused review, we present an underestimated compartment, the blood–brain barrier, which is compromised during MS and becomes permeable to leukocytes infiltrating the central nervous system. This barrier has the potential to offer new therapeutic strategies and is easily accessible for drugs. We highlight this paradigm using the example of the therapeutic anti-Reelin strategy we have developed. Reelin is a plasma protein that regulates the expression of adhesion markers on the endothelial surface, thus promoting the infiltration of inflammatory cells and propagating inflammation. Building Back a Better Blood–Brain Barrier (the “6B” strategy) may have advantages compared to actual immunosuppressive drugs because it restores a physiological function rather than suppressing the immune system. Full article

Bacterial lipopolysaccharides (LPS), also referred to as endotoxins, are major outer surface membrane components present on almost all Gram-negative bacteria and are major determinants of sepsis-related clinical complications including septic shock. LPS acts as a strong stimulator of innate or natural immunity in a wide variety of eukaryotic species ranging from insects to humans including specific effects on the adaptive immune system. However, following immune stimulation, lipopolysaccharide can induce tolerance which is an essential immune-homeostatic response that prevents overactivation of the inflammatory response. The tolerance induced by LPS is a state of reduced immune responsiveness due to persistent and repeated challenges, resulting in decreased expression of pro-inflammatory modulators and up-regulation of antimicrobials and other mediators that promote a reduction of inflammation. The presence of environmental-derived LPS may play a key role in decreasing autoimmune diseases and gut tolerance to the plethora of ingested antigens. The use of LPS may be an important immune adjuvant as demonstrated by the promotion of IDO1 increase when present in the fusion protein complex of CTB-INS (a chimera of the cholera toxin B subunit linked to proinsulin) that inhibits human monocyte-derived DC (moDC) activation, which may act through an IDO1-dependent pathway. The resultant state of DC tolerance can be further enhanced by the presence of residual E. coli lipopolysaccharide (LPS) which is almost always present in partially purified CTB-INS preparations. The approach to using an adjuvant with an autoantigen in immunotherapy promises effective treatment for devastating tissue-specific autoimmune diseases like multiple sclerosis (MS) and type 1 diabetes (T1D). Full article