Similar to SIRS, there is evidence of OS involvement in KD, Some OS biomarkers, such as reactive oxygen metabolites (ROM), were increased in patients with KD naïve to treatment and favorably decreased in cases responding to treatment, in contrast to non-responding patients ( 80). It has also been described that there is a late increase in plasma levels of malondialdehyde and hydroperoxide after acute disease in patients with KD ( 81).

Elisia I, et al. (2020). The effect of smoking on chronic inflammation, immune function and blood cell composition. Omega-3 fish oils, containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), 1-3 grams daily. Ferrara G, Giani T, Caparello MC, Farella C, Gamalero L, Cimaz R. Anakinra for Treatment-Resistant Kawasaki Disease: evidence from a literature review. Paediatr Drugs Dec. 2020;22(6):645–52. https://doi.org/10.1007/s40272-020-00421-3. Being fat increases inflammation because adipose cells, particularly those around the tummy, make large amounts of IL-6 and CRP. As blood sugar levels increase, so do IL-6 and CRP. Being overweight and having high blood sugar levels increase the risk of heart disease, very likely because of the undercurrent of inflammation.Neutrophils, which target microorganisms in the body, can also damage host cells and tissues [ 74]. Neutrophils are key mediators of the inflammatory response, and program antigen presenting cells to activate T cells and release localized factors to attract monocytes and dendritic cells [ 7]. Macrophages are important components of the mononuclear phagocyte system, and are critical in inflammation initiation, maintenance, and resolution [ 75]. During inflammation, macrophages present antigens, undergo phagocytosis, and modulate the immune response by producing cytokines and growth factors. Mast cells, which reside in connective tissue matrices and on epithelial surfaces, are effector cells that initiate inflammatory responses. Activated mast cell release a variety of inflammatory mediators, including cytokines, chemokines, histamine, proteases, prostaglandins, leukotrienes, and serglycin proteoglycans [ 76]. Maroon JC, et al. (2006). Omega-3 fatty acids (fish oil) as an anti-inflammatory: An alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. In addition, viral proteins and inflammatory cytokines induce neutrophil activation, leading to ROS secretion and the formation of neutrophil extracellular traps (NETs) ( 24, 25). HMGB1, which is triggered by ROS, may also play a role in NET activation ( 26). Increased concentration of NETs has been observed in plasma, tracheal aspirate, and lung specimens of autopsies from COVID-19 patients ( 27). NETs further promote and sustain the local inflammation. A high concentration of NETs positively correlates with sepsis severity and organ dysfunction, and they have been shown to contribute to immunothrombosis in the course of inflammatory response ( 27– 30). These early events that involve interaction between SARS-CoV-2 with host cells including, innate immune cells play an important role in inducing endothelial damage, acute lung injury, disruption of lung structure associated with pulmonary edema and pneumonia, multi-organ damage and death in COVID-19 disease. Adaptive Immunity https://www.arthritis.org/health-wellness/healthy-living/nutrition/anti-inflammatory/anti-inflammatory-diet Microscopic polyangiitis is a rare and potentially serious long-term type of vasculitis that most often develops in middle-aged people.

On the other hand, antioxidant markers are decreased in patients with KD in acute stages, such as the antioxidant power ( 82). Also, there is evidence of an association between the presence of manganese superoxide dismutase ( MnSOD) rs5746136 polymorphism and susceptibility to KD ( 83). Other studies have proposed the use of antioxidant substances as adjuvant therapy for these patients; in particular, berberine exerts a protective effect against KD-induced damage of human coronary artery endothelial cells through the decrease of OS markers ( 84). Granulomatosis with polyangiitis is a serious condition that can be fatal if left untreated, as it can lead to organ failure. Harthan AA, Nadiger M, McGarvey JS, et al. Early combination therapy with immunoglobulin and steroids is associated with shorter ICU length of stay in Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19: a retrospective cohort analysis from 28 U.S. hospitals. Pharmacotherapy Jul. 2022;42(7):529–39. https://doi.org/10.1002/phar.2709. Some of these pathways increase the activity of type I IFN and inflammatory cytokines ( 38). After viral replication, there is an increase in the levels of TNF-α, IFN-γ and IL-4, which leads to the activation of cellular pro-inflammatory pathways ( 39). Importantly, in addition to promoting cytotoxicity, ROS and RNS can initiate and amplify inflammatory pathways through the regulation of gene expression via nuclear factor kappa B (NF-κB) ( 40). Moreover, the presence of ROS, such as hydrogen peroxide (H 2O 2), usually functions as a stimulus for the activation of inflammatory responses ( 41, 42). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher’s NoteOS has been implicated in different pathologies as a triggering factor of the pathophysiological process, such as kidney disease ( 27), diabetes ( 28), rheumatic autoimmune disease ( 24, 29) In addition to its role in these chronic diseases, the production of ROS plays an important role in the defense mechanisms against infectious diseases such as hepatitis B, C and D, herpes, influenza, tuberculosis and leprosy ( 30– 33). However, excessive ROS production increases the inflammatory response and in turn can increase cellular injury induced by viral infection ( 34). Evidence suggests that OS is involved in acute bronchiolitis caused by respiratory syncytial virus, considering elevated plasma levels of oxidized glutathione (GSSG) and the antioxidant enzyme glutathione peroxidase (GPx) as biomarkers of severity in these patients ( 35). The treatment of children with multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection involves immunomodulatory therapies such as IVIG and steroids. Anakinra, an interleukin-1 receptor inhibitor, has also been used, but its effectiveness is not established yet. As optimal regimens for MIS-C remain unknown, we aimed to assess the effect of anakinra in reducing hospital stay in patients with MIS-C. Methods Cytokine release syndrome, also known as cytokine storm, correlates with COVID-19 severity and has been recognised as a major cause of mortality among COVID-19 patients ( 43). It is defined as a life-threatening condition involving the excessive cytokine and chemokines produced by the dysregulation of the immune response ( 43). Considering that these inflammatory mediators are interdependent and can be both protective and pathologic, distinguishing them can be challenging. In the serum of COVID-19 patients with cytokine storm, various raised cytokine levels are reported. This includes IL-1β, interleukin-6 (IL-6), tumor necrosis factor (TNF), macrophage inflammatory protein (MIP) 1α and 1β, interferon-γ, inducible protein 10 (IP-10), and VEGF ( 19, 44).

Microscopic polyangiitis is usually treated with steroid medicine or other medicines that reduce the activity of the immune system.Strand V, et al. (2017). Immunogenicity of biologics in chronic inflammatory diseases: A systematic review. Soon after the trigger of the innate immune response, antibody-producing B cells, CD4+ T cells and CD8+ T cells of the adaptive immunity are primed to control pathogenic infection. While innate immunity is intrinsically involved in COVID-19 immunopathogenesis, there is limited evidence supporting the pathogenic phenomenon of adaptive immunity. In contrast to massive innate cytokines or chemokines associated with immunopathology, elevated T cells are therapeutic and do not worsen the disease. Seroconversion is shown to occur in more than 90% of COVID-19 patients a few weeks post-infection ( 31). Compared to CD8+ T cells, CD4+ T cells present a greater antiviral effect towards SARS-CoV-2 infection and better control of disease severity ( 32, 33). The primary targets of CD4+ T cells include the highly expressed spike, M and nucleocapsid antigen, with significant specificity for nsp3, nsp4 and ORF8 ( 32). Meanwhile, CD8+ T cells showed a slightly different immunoreactivity, with spike protein, nucleocapsid, M, nsp6, ORF8 and ORF3a being the target antigens ( 32). Inflammation is the immune system's response to harmful stimuli, such as pathogens, damaged cells, toxic compounds, or irradiation [ 1], and acts by removing injurious stimuli and initiating the healing process [ 2]. Inflammation is therefore a defense mechanism that is vital to health [ 3]. Usually, during acute inflammatory responses, cellular and molecular events and interactions efficiently minimize impending injury or infection. This mitigation process contributes to restoration of tissue homeostasis and resolution of the acute inflammation. However, uncontrolled acute inflammation may become chronic, contributing to a variety of chronic inflammatory diseases [ 4].