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The Modulation of IL-6 Levels by Natural Products in Arthritis-Like Animal Models
Published in Parimelazhagan Thangaraj, Lucindo José Quintans Júnior, Nagamony Ponpandian, Nanophytomedicine, 2023
Fabiolla R.S. Passos, Marilia M. Rezende, Sathiyabama R. Gandhi, Bruno A.F. Silva, Andreza G.B. Ramos, Irwin R.A. Menezes, Parimelazhagan Thangaraj, Lucindo José Quintans Júnior, Jullyana S.S. Quintans
Secondary metabolites present in medicinal plants can modulate the production or expression of anti-inflammatory substances, such as cytokines (Khanna et al., 2007). The cytokine interleukin-6 (IL-6) plays a key role in the regulation of arthritic inflammation including in the differentiation and proliferation of T and B cells, inflammatory pannus formation (Paleolog, 2002), increasing the number of neutrophils (Lally et al., 2005) and osteoclast activation (McInnes and Schett, 2007). Choy and Calabrese (2018) hypothesized that IL-6 is a primary mediator of joint pain through direct regulation in the nociceptive nervous system. These findings led to the notion that targeting IL-6 might constitute a novel treatment strategy for various diseases. This resulted in the development of tocilizumab, a humanized anti-IL-6R monoclonal antibody of the IgG1 class (Sato et al., 1993) that blocks IL-6-mediated signal transduction by inhibiting IL-6 binding to transmembrane and sIL-6R. This systematic review was carried out to summarize the findings of studies using arthritis-like animal models to examine the potential of NPs as modulators of IL-6 to support the development of effective new treatment options for the disease.
Pro- and Anti-Inflammatory Cytokine Signaling within 3D Tissue Models
Published in Karen J.L. Burg, Didier Dréau, Timothy Burg, Engineering 3D Tissue Test Systems, 2017
Stephen L. Rego, Tian McCann, Didier Dréau
Interleukin-6 (IL6) is an inflammatory cytokine, which belongs to a superfamily that includes oncostatin M and leukemia inhibitory factor. IL-6 is secreted by monocytes, fibroblasts, B cells, and T cells (Akira et al. 1990). IL6 is critical in inducing fever in response to pathogens. Cellular signaling of IL6 requires binding of IL6 to its receptor (IL6R), which in turn activates the coreceptor glycoprotein 130 (gp130), thus, leading to signaling through the JAK/STAT pathway (Schneiders et al. 2015). Interestingly, the IL6R can be shed from cells by the enzyme tumor necrosis factor converting enzyme (TACE) and modulate the inflammatory response through trans-signaling (Rego et al. 2014). Along with its inflammatory properties, IL6 also acts as an anti-inflammatory factor in muscle (Scheller et al. 2011).
Aloe vera Gel Extract
Published in Parimelazhagan Thangaraj, Phytomedicine, 2020
S. Govindarajan, Spoorthy N. Babu, Ayesha Noor
In this study, the anti-inflammatory potential of the Aloe vera extract with respect to its ability to reduce the damage caused through oxidative stress was evaluated. An important aspect of the inflammation is that there is a disturbance in the homeostasis of the anti-inflammatory and pro-inflammatory cytokines (Kalaiselvan and Rasool 2015). The increased levels of pro-inflammatory cytokines, such as TNF-α, IL-6, monocyte chemoattractant protein 1, etc. propagate the progression of the inflammation through the infiltration of neutrophils, leading to destruction and damage of the joints and bones (Zhang et al. 2013). In this study, we have observed the levels of TNF-α, IL-6, and sPla2 in inflammation and the effect of the Aloe vera gel extract on these inflammatory mediators. TNF-α is one of the pleiotropic cytokines that is seen mostly in cases of inflammatory disorders. Cells such as synoviocytes and T-cells produce pro-inflammatory cytokines upon activation, thus leading to synovial inflammation in the joints (Kalaiselvan and Rasool 2015). Another pleiotropic cytokine is IL-6, which plays a crucial role in the maturation of B cells. IL-6 is also involved in the production of the auto-antibodies and plays a role in arthritic progression (Srirangan and Choy 2010). IL-6 is involved in the progression of joint inflammation through elevated levels of Vascular Endothelial Growth Factor (VEGF). It was observed in this study that the levels of TNF-α and IL-6 were elevated in the plasma of the inflammatory control rats. Oral feeding of the Aloe vera extract has shown a significant reduction in the levels of these inflammatory cytokines (Figure 15.3b and c). There are reports which suggest that phenolics such as quercetin, catechin, rutin, kaempferol, myricetin, and luteolin have anti-inflammatory properties which may help in the reduction of the inflammation and alleviation of rheumatoid arthritis (Lee and Kim 2010). The presence of the phenolic constituents, listed in Table 15.1, in the Aloe vera gel extract may play a role in decreasing the levels of TNF-α and IL-6, thereby leading to the reduction in inflammation as seen in the reduction of paw edema (Figure 15.3a).
Preliminary investigation of a hypertonic saline nasal rinse as a hygienic intervention in dairy workers
Published in Journal of Occupational and Environmental Hygiene, 2023
Grant Erlandson, Sheryl Magzamen, Julia L. Sharp, Sanchayita Mitra, Kenneth Jones, Jill A. Poole, Mary Bradford, Matthew Nonnenmann, Stephen J. Reynolds, Joshua W. Schaeffer
In contrast, HTS nasal lavage did not reduce commonly measured pro-inflammatory cytokine levels as has been reported in earlier studies. The aforementioned studies also observed decreases in IL-6 and TNF-α production with HTS while our results indicate an increase in IL-6 and partially in IL-8 (Oreopoulos et al. 2000; Rizoli et al. 2006). IL-6 has been previously recognized as a pro-inflammatory mediator. Increased IL-6 levels in the serum and/or bronchoalveolar lavage fluid have been associated with asthma and COPD severity (Rincon and Irvin 2012; Ferrari et al. 2013). However, increases in IL-6 occur in active asthmatics even when TNF-α and IL-1β were not increased, which has led others to propose that IL-6 is not simply a pro-inflammatory marker but may be the result of “activated” airway epithelial cells (Rincon and Irvin 2012). Moreover, it has also been shown that airway inflammatory consequences induced by swine confinement facility organic dust extract exposure, which included airway neutrophil influx, cytokine/chemokine release, and lung pathology, were not reduced in IL-6 deficient mice as compared to wild type (Wells et al. 2017). Thus, the significance of increased IL-6 following hypertonic saline solution administration necessitates further evaluation to fully understand its significance, particularly following large animal farming dust exposures. It is possible that a decrease in TNF-α existed in the treatment group, but too many samples were below the analytical limit of detection to adequately analyze.
Risk modelling further implicates the angiogenesis pathway in anterior cruciate ligament ruptures
Published in European Journal of Sport Science, 2022
Masouda Rahim, Miguel Lacerda, Malcolm Collins, Michael Posthumus, Alison V. September
Interleukin-1, is involved in a variety of cellular activities, including cell proliferation and differentiation, angiogenesis and apoptosis. In particular, IL-1β, encoded by the IL1B gene, is a pro-inflammatory cytokine responsible for activating numerous downstream signalling cascades (Thampatty et al., 2007; Yang et al., 2005). IL-6, encoded by IL6, is a pleiotropic cytokine with both pro-inflammatory and anti-inflammatory effects. It acts on a wide range of tissues with roles in apoptosis, cell growth and differentiation, as well as angiogenesis. Elevated IL-6 expression was reported in tissues that undergo angiogenesis and IL-6 was also shown to induce VEGF levels to a similar degree as has been observed in hypoxic states (Cohen et al., 1996). IL-6 exerts its biological effects by binding and forming a complex with the interleukin-6 receptor (IL6R) and therefore the receptor may also play a necessary role in IL-6 induced angiogenesis.
Dietary ingestion of 2-aminoanthracene (2AA) and the risk for type-1 diabetes (T1D)
Published in Journal of Environmental Science and Health, Part A, 2020
Isaiah Seise, Zachary A. Pilz, Moses Yeboah Kusi, Bethany Bogan, Brittany Jean McHale, Worlanyo E. Gato
Inflammatory cytokines and apoptosis genes that play various roles in relation to T1D were quantified in the pancreas of all three groups. Upregulation of IL-6, IL-7, and IL-1β in the low and high 2AA concentration groups relative to the control group was observed. It is reasonable to note that the overexpression of these pro-inflammatory proteins was an indication of a more pronounced autoimmune activity in the pancreas. Cells produce small proteins such as cytokines which have peculiar effects on communication and interaction among cells.[17] Cytokines are key intermediaries of inflammation through guiding of innate and adaptive immune responses and tissue damage.[18] Autoimmune disorders such as rheumatoid arthritis and multiple sclerosis have been reported to be associated with overexpression of IL-6.[18] IL-1β secreted by macrophages in the pancreas attract immune cells including dendritic cells and T lymphocytes into the islets which then attack the β-cells.[19] IL-1β can increase the susceptibility of β-cells to apoptosis by raising the production of pro-apoptosis proteins including Fas receptor.[19] Also, IL-7 was overexpressed in the pancreas of rats that ingested 2AA contaminated diets. Recent studies have revealed that homeostatic IL-7 can increase autoreactive T-cell differentiation and expansion.[20] The destruction of β-cells and the pathogenesis of T1D are mediated by T-cells. The upregulation of IL-7 will, therefore, result in an increased presence of T-cells in the pancreas of rats in the treated groups.