Interleukin-1 beta has atheroprotective effects in advanced atherosclerotic lesions of mice

Despite decades of research, our understanding of the processes controlling late-stage atherosclerotic plaque stability remains poor. A prevailing hypothesis is that reducing inflammation may improve advanced plaque stability, as recently tested in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, in which post-myocardial infarction subjects were treated with an IL-1β antibody. Here, we performed intervention studies in which smooth muscle cell (SMC) lineage-tracing Apoe-/- mice with advanced atherosclerosis were treated with anti-IL-1β or IgG control antibodies. Surprisingly, we found that IL-1β antibody treatment between 18 and 26 weeks of Western diet feeding induced a marked reduction in SMC and collagen content, but increased macrophage numbers in the fibrous cap. Moreover, although IL-1β antibody treatment had no effect on lesion size, it completely inhibited beneficial outward remodeling. We also found that SMC-specific knockout of Il1r1 (encoding IL-1 receptor type 1) resulted in smaller lesions nearly devoid of SMCs and lacking a fibrous cap, whereas macrophage-selective loss of IL-1R1 had no effect on lesion size or composition. Taken together, these results show that IL-1β has multiple beneficial effects in late-stage murine atherosclerosis, including promotion of outward remodeling and formation and maintenance of an SMC- and collagen-rich fibrous cap

Optimized Nanostructured Lipid Carriers Integrated into in situ Nasal Gel for Enhancing Brain Delivery of Flibanserin [Retraction]

Fahmy UA, Ahmed OAA, Badr-Eldin SM, et al. Int J Nanomedicine. 2020;15:5253-5264. The Editor and Publisher of International Journal of Nanomedicine are retracting the above published article. An investigation by the Publisher, found overlap in images from Figure 6 of the published article above and the images from Figure 6 of the following published article: Ahmed OAA, Fahmy UA, Badr-Eldin SM, et al. Application of Nanopharmaceutics for Flibanserin Brain Delivery Augmentation Via the Nasal Route. Nanomaterials. 2020; 10(7):1270 (https://doi.org/10.3390/nano10071270). Specifically, this included: From the published article above, Figure 6B, plain in situ gel group, and 6D, optimized FLB-NLC in situ gel group, are the same images as Figure 6D, rats treated with optimized FLB-TRF hydrogel (gp4) and 6C, rats treated with raw FLB loaded in hydrogel (gp3), respectively, from Ahmed et al, 2020. Furthermore, the images in Figure 6 of the published article above are derived from the same image but used to describe different results. Specifically, this included: From the published article above, Figure 6A, Control untreated group; 6B, plain in situ gel group; 6C, raw FLB loaded in situ gel group and 6D, optimized FLB-NLC in situ gel group, are all derived from the same image but used to describe different results. The authors cooperated with the investigation and provided data and associated documents concerning the histopathological experiments from the reported study. However, the Editor and Publisher determined that the evidence provided did not establish sufficient justification for the duplication. Therefore, the Editor and Publisher are retracting the article. The authors have agreed to retract the article and have informed the Publisher that the first author, Usama A Fahmy, takes responsibility for the error which occurred. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”

Generation of a Novel T Cell Specific Interleukin-1 Receptor Type 1 Conditional Knock Out Mouse Reveals Intrinsic Defects in Survival, Expansion and Cytokine Production of CD4 T Cells

Interleukin-1 (IL-1) plays a crucial role in numerous inflammatory diseases via action on its only known signaling IL-1 receptor type 1 (IL-1R1). To investigate the role of IL-1 signaling in selected cell types, we generated a new mouse strain in which exon 5 of the Il1r1 gene is flanked by loxP sites. Crossing of these mice with CD4-Cre transgenic mice resulted in IL-1R1 loss of function specifically in T cells. These mice, termed IL-1R1ΔT, displayed normal development under steady state conditions. Importantly, isolated CD4 positive T cells retained their capacity to differentiate toward Th1 or Th17 cell lineages in vitro, and strongly proliferated in cultures supplemented with either anti-CD3/CD28 or Concanavalin A, but, as predicted, were completely unresponsive to IL-1β administration. Furthermore, IL-1R1ΔT mice were protected from gut inflammation in the anti-CD3 treatment model, due to dramatically reduced frequencies and absolute numbers of IL-17A and interferon (IFN)-γ producing cells. Taken together, our data shows the necessity of intact IL-1 signaling for survival and expansion of CD4 T cells that were developed in an otherwise IL-1 sufficient environment