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This work evaluated aspects of the immune response of BALB/c mice infected with Corynebacterium pseudotuberculosis (T1 and C57). The fifteen BALB/c mice were euthanized after 70 days of infection and morphologically evaluated, also analyzing the innate and adaptive immune responses. The C57 strain induced more pronounced morphological changes than the T1 strain. There was an increase in CD4 + and CD8 + T cells identified during infection with the C57 strain. Cytokines of the inflammatory profile IL-1α and IL-6 and regulatory IL-13 and IL-10 presented significant differences. Cytokines IL-2, IL-4, INF-γ, IL-22, IL-21, and IL-27 did not differ significantly between groups. The obtained results contribute to a better understanding of the type of response and the immunological mechanisms involved during infection with different strains of C. pseudotuberculosis., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024. Published by Elsevier Ltd.)

The amyloid beta (Aβ) peptide is believed to play a central role in Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. However, the natural, evolutionarily selected functions of Aβ are incompletely understood. Here, we report that nanomolar concentrations of Aβ act synergistically with known cytokines to promote pro-inflammatory activation in primary human astrocytes (a cell type increasingly implicated in brain aging and AD). Using transcriptomics (RNA-seq), we show that Aβ can directly substitute for the complement component C1q in a cytokine cocktail previously shown to induce astrocyte immune activation. Furthermore, we show that astrocytes synergistically activated by Aβ have a transcriptional signature similar to neurotoxic "A1" astrocytes known to accumulate with age and in AD. Interestingly, we find that this biological action of Aβ at low concentrations is distinct from the transcriptome changes induced by the high/supraphysiological doses of Aβ often used in in vitro studies. Collectively, our results suggest an important, cytokine-like function for Aβ and a novel mechanism by which it may directly contribute to the neuroinflammation associated with brain aging and AD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Smoking is an important risk factor for the development of chronic obstructive pulmonary disease (COPD) and viral infections are believed to be major triggers of exacerbations, which periodically lead to a worsening of symptoms. The pro-inflammatory IL-1 family members IL-1α and IL-1β are increased in COPD patients and might contribute to disease pathology. We investigated whether individual or combined inhibition of these cytokines reduced lung inflammation in cigarette smoke (CS)-exposed and H1N1-infected BALB/c mice. Animals were treated with individual or combined antibodies (Abs) directed against IL-1α, IL-1β or IL-1R1. Cells in BAL fluid and cytokines/chemokines in lung homogenate were determined. The viral load was investigated. Blocking IL-1α had significant suppressive effects on total cells, neutrophils, and macrophages. Furthermore, it reduced KC levels significantly. Blocking of IL-1β did not provide significant activity. In primary human bronchial epithelial air-liquid-interface cell cultures infected with H1N1, IL-1α Abs but not IL-1β Abs reduced levels of TNF-α and IL-6. Concomitant usage of Abs against IL-1α/IL-1β revealed strong effects in vivo and reduced total cells, neutrophils and macrophages. Additionally, levels of KC, IL-6, TNF-α, MCP-1, MIP-1α and MIP-1β were significantly reduced and ICAM-1 and MUC5 A/C mRNA expression was attenuated. The viral load decreased significantly upon combined IL-1α/IL-1β Ab treatment. Blocking the IL-1R1 provided significant effects on total cells, neutrophils and macrophages but was inferior compared to inhibiting both its soluble ligands IL-1α/IL-1β. Our results suggest that combined inhibition of IL-1α/IL-1β might be beneficial to reduce CS/H1N1-induced airway inflammation. Moreover, combined targeting of both IL-1α/IL-1β might be more efficient compared to individual neutralization IL-1α or IL-1β or inhibition of the IL-1R1., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers., Methods: We conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates., Results: Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06-3.93), p-trend=0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14-4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06-4.63), p-trend=0.04]. Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96-3.61), p-trend=0.05]. In analyses restricted to serous ovarian cancer (n=83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14-11.14), p-trend=0.008; IL-8 T3 vs. T1: 3.05 (1.09-8.51), p-trend=0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5years before diagnosis (n=56)., Conclusion: These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer., (Published by Elsevier Inc.)

Although the IL-1α molecule has long been recognized, information about its distinct role in various diseases is limited, since most clinical studies have focused on the role of IL-1β. Despite triggering the same IL-1 receptor as does IL-1β, there is, however, a distinct role for IL-1α in some inflammatory diseases. IL-1α is a unique cytokine since it is constitutively present intracellularly in nearly all resting non-hematopoietic cells in health as well as being up-regulated during hypoxia. During cell necrosis, IL-1α functions as an alarm molecule and thus plays a critical role early in inflammation. Following its release from damage tissue cells, IL-1α mediates neutrophil recruitment to the site of injury, inducing IL-1β, other cytokines and chemokines from surrounding resident cells. Another unique attribute of IL-1α is its nuclear localization sequence present in the N-terminal half of the precursor termed the propiece. The IL-1α propiece translocates into the nucleus and participates in the regulation of transcription. Therefore, IL-1α, like IL-1 family members IL-33 and IL-37, is a 'dual-function' cytokine binding to chromatin as well as to its cell surface receptor. Some cancer cells can express membrane IL-1α, which can increase immunogenicity of tumor cells and serve in anti-tumor immune surveillance and tumor regression. However, in the tumor microenvironment, precursor IL-1α released from dying tumor cells is inflammatory and, similar to IL-1β, increases tumor invasiveness and angiogenesis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Deficiency of the IL-1 receptor antagonist (DIRA) is a recently described rare autoinflammatory disease, caused by loss of function mutations in IL1RN leading to the unopposed activation of the IL-1 pathway. We describe a novel nonsense mutation in the IL1RN gene, associated with early intrauterine onset, death and multiorgan involvement in a prematurely born baby. The protein prediction model indicated that the novel Q119X mutation would result in a nonfunctional protein by impairing the ability of the IL-1Ra to bind and antagonize signaling through the IL-1R. Since the disorder may mimic severe bacterial infections and the treatment with anakinra is life saving, we intend to raise awareness of the syndrome and the possibility of a founder mutation that may lead to the diagnosis of additional cases in Turkey. The clinical suspicion of DIRA is critical to avoid improper management of the patients with antibiotics alone and death from multiorgan failure., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Interleukin (IL)-1 is a cytokine that plays a major role in inflammatory responses in the context of infections and immune-mediated diseases. IL-1 refers to two different cytokines, termed IL-1alpha and IL-1beta, produced from two genes. IL-1alpha and IL-1beta are produced by different cell types following stimulation by bacterial products, cytokines, and immune complexes. Monocytes/macrophages are the primary source of IL-1beta. Both cytokines do not possess leader peptide sequences and do not follow a classical secretory pathway. IL-1alpha is mainly cell associated, whereas IL-1beta can be released from activated cells after cleavage of its amino-terminal region by caspase-1. IL-1 is present in the synovial tissue and fluids of patients with rheumatoid arthritis. Several in vitro studies have shown that IL-1 stimulates the production of mediators such as prostaglandin E(2), nitric oxide, cytokines, chemokines, and adhesion molecules that are involved in articular inflammation. Furthermore, IL-1 stimulates the synthesis and activity of matrix metalloproteinases and other enzymes involved in cartilage destruction in rheumatoid arthritis and osteoarthritis. The effects of IL-1 are inhibited in vitro and in vivo by natural inhibitors such as IL-1 receptor antagonist and soluble receptors. IL-1 receptor antagonist belongs to the IL-1 family of cytokines and binds to IL-1 receptors but does not induce any intracellular response. IL-1 receptor antagonist inhibits the effect of IL-1 by blocking its interaction with cell surface receptors. The use of IL-1 inhibitors in experimental models of inflammatory arthritis and osteoarthritis has provided a strong support for the role of IL-1 in the pathogeny of these diseases. Most importantly, these findings have been confirmed in clinical trials in patients with rheumatic diseases. Additional strategies aimed to block the effect of IL-1 are tested in clinical trials.