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Myocarditis
Published in Mary N. Sheppard, Practical Cardiovascular Pathology, 2022
COVID-19 is less frequent in children, with a milder course. More severe disease is now reported in a minority of children. They appear to have a cytokine storm, reflected clinically by HF, pneumonia, GI, neurological and renal features, associated with elevated CRP levels, ferritin and cytokines (IL-1, TNFα and IL-6) and many require intensive care support. It is interesting that some of these children met the biological criteria for macrophage-activation syndrome (MAS) highlighting the role of macrophages. This is now called a systemic inflammatory syndrome mimicking Kawasaki disease (KD), temporally associated with SARS-CoV-2 infection (Kawa-COVID-19).18 No EMB or autopsy findings are reported and, thankfully, all survive.
Neuro–Endocrine–Immune Dysfunction in the Chronic Pain Patient
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Another pathway used by the central nervous system to communicate with the immune system is via a neuropeptidergic pathway. When nociceptors are activated, the axons themselves release neuropeptides that have been noted to further impact the activity of the neurons. Substances such as CGRP, SP, adrenomedullin, neurokinin A and BV, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) are examples of these type of neuropeptides. These neuropeptides also modulate innate and adaptive immune cells. Mast cell degranulation increases. Neutrophil activation and chemotaxis increase. T-cell activation and proliferation increase. Macrophage activation and phagocytosis capability increase.8
AIDS and other acquired immunodeficiencies
Published in Gabriel Virella, Medical Immunology, 2019
John W. Sleasman, Gabriel Virella
Macrophage activation. Macrophages harvested from patients with burn injury appear to be in a state of activation, releasing increased amounts of interleukin (IL)-1, tumor necrosis factor (TNF), IL-6, transforming growth factor (TGF-β), and prostaglandin 2 (PGE2). These same cytokines are measured in increased levels in the circulation of patients with severe burns. Of these cytokines, IL-6 has been shown to be the one that is consistently elevated after thermal injury. It has been proposed that this state of activation increases the response of macrophages to other stimuli, such as endotoxin, therefore increasing the susceptibility of burn patients to sepsis.
Scavenger Receptor A1 Signaling Pathways Affecting Macrophage Functions in Innate and Adaptive Immunity
Published in Immunological Investigations, 2022
Elizabeth Linares-Alcántara, Fela Mendlovic
Macrophages are highly heterogeneous and may be differentially activated, i.e., M1 or classically activated and M2 or alternatively activated depending on their microenvironment (Stout et al. 2005). These two phenotypes are involved in different stages of the immune response and express diverse cytokines, chemokines, and surface receptors. The M1 macrophages differentiate in the presence of INF-γ and IL-12, are characterized by the production of proinflammatory cytokines IL-1β, IL-6, TNF-α, express iNOS, and are mainly involved in anti-microbial and anti-tumor activity. On the other hand, M2 macrophages respond to IL-4, IL-10, IL-13 and glucocorticoids and produce IL-10, Arginase I (Arg-1) that competes with iNOS, as well as galectin-3 (Gal-3), mannose receptor, chitinase-like lectin (YM1) and resistin-like secreted protein (FIZZ1). M2 macrophages are involved in the anti-helminth responses, resolution of inflammation and tissue remodeling (Sica and Mantovani 2012). The balance in macrophage activation is essential for a coordinated immune response. Both macrophage phenotypes have been implicated in disease and homeostasis.
Bispecific CAR T-cells for B-cell Malignancies
Published in Expert Opinion on Biological Therapy, 2022
In a phase 1 study, 17 patients with R/R B-ALL and 22 patients with R/R large B-cell lymphoma (LBCL) received CD19-22BB.zCAR infusion in a 3 + 3 dose escalation followed by a dose expansion phase (Tables 2 and 3) [21]. The bispecific CAR comprised a single cistron encoding the anti-CD19 murine FMC63 single-chain variable fragment (scFv) and fully human anti-CD22 m971 scFv. CRS was reported in 76% of patients, with two patients having grade 3 or higher. Thirty-seven percent of patients had neurotoxicity, four patients with grade 3 or higher. Two patients with grade ≥3 neurotoxicity also had macrophage activation syndrome. All adverse effects resolved with treatment. In LBCL, the best ORR and CRR at any time were 62% and 29%, respectively, and the median OSS and PFS were 22.5 and 3.2 months, respectively. On the other hand, 82% patients with B-ALL achieved CR and three achieved PR at 28 days while median OS and PFS were 11.8 and 5.8 months, respectively. In patients who relapsed, CD19 expression was low or absent but they continued to express CD22. The likely cause of CD22+ relapse could be due to a lower cytokine production by CD22 targeting versus CD19.
Spotlight on liver macrophages for halting injury and progression in nonalcoholic fatty liver disease
Published in Expert Opinion on Therapeutic Targets, 2022
Tea Lund Laursen, Anders Mellemkjær, Holger Jon Møller, Henning Grønbæk, Konstantin Kazankov
The world prevalence of nonalcoholic fatty liver disease is approximately 25% with regional differences and is the most common liver disease. Due to the increase in patients with metabolic risk factors and metabolic syndrome with development of obesity and T2DM, there has been a significant increase in NAFLD and an associated increase in liver-related morbidity and mortality in addition to cardiovascular and cancer-related mortality. There is an unmet need for a better understanding of disease pathogenesis from fat accumulation to disease progression with inflammation, fibrosis, progression to cirrhosis and development of hepatocellular carcinoma. Particularly, the transition from simple steatosis to inflammation is important and, in this context, macrophages seem to play an important role both for disease progression but also as treatment targets. In addition, biomarkers of macrophage activation may be used as companion biomarkers for interventions targeting macrophages directly or indirectly and as a prognostic capacity.