scholarly journals Immunomodulatory and anti-inflammatory effects of N-acetylcysteine in ovalbumin-sensitized rats

Author(s):  
Maha M. Abdel-Fattah ◽  
Abeer A. A. Salama ◽  
Basim A. S. Messiha

Abstract Background Pro-inflammatory cytokines such as interleukin-5 (IL-5) and tumor necrosis factor-alpha (TNF-α) as well as immunoglobulin-E (IgE) appear to play a role in asthma. N-acetylcysteine (NAC), an antioxidant, might have clinical benefits in asthma prevention. The possible preventive effects of NAC against experimentally induced asthma in rats are investigated. The rats were allocated into five groups: a normal control, asthma control, a standard dexamethasone (DEXA, 1 mg/kg, orally) group, and two NAC groups (300 and 500 mg/kg, orally, respectively). Ovalbumin (OVA) sensitization was used to trigger asthma, which was then followed by an intra-nasal challenge. Test gents were administrated for 14 days before the challenge and during the three challenge days (20, 21, and 22). The tidal volume (TV) and peak expiratory flow rate (PEFR) as respiratory functions were determined. The pro-inflammatory cytokines as IL-5 and TNF-α were evaluated in lung homogenate. Serum IgE and absolute eosinophil count (AEC) in bronchoalveolar lavage fluid (BALF) were measured. In addition, the oxidative markers in lung tissue and nitrosative marker in BALF were assessed; finally, lungs were isolated for histopathological study. Results NAC restored lung functions, inhibited the asthma-dependent increase in TNF-α, IL-5, IgE, AEC, nitric oxide, and malondialdehyde levels. NAC further re-established lung glutathione content and superoxide dismutase activity, resulting in milder overall lung pathology. Conclusions Experimental bronchial asthma may be protected by NAC. The anti-asthmatic potential of NAC may be explained by its suppressant influence on IgE antibody formation, pro-inflammatory cytokines production, eosinophil infiltration, and oxidative stress.

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3374
Author(s):  
Mohamed Abdo Rizk ◽  
Shimaa Abd El-Salam El-Sayed ◽  
Doaa Salman ◽  
Basma H. Marghani ◽  
Hossam Elshahat Gadalla ◽  
...  

In this study, we have investigated the impact of vitamin C on the production of pro-inflammatory cytokines (interleukin 1 β (IL-1 β), interleukin 6 (IL-6), interleukin 12p40 (IL-12p40), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α)) in lambs naturally infected by pneumonic pasteurellosis. Of 37 lambs, 18 lambs were identified to have pneumonic pasteurellosis and randomly allocated into two equal groups. Single subcutaneous dose of tulathromycine alone (2.5 mg kg−1) or tulathromycine combined with vitamin C (3 gm kg−1) were administrated to the diseased lambs. The serum levels of IL-1β, IL-6, IFN-γ, and TNF-α were returned to the normal levels in pneumonic lambs treated with the combination therapy. The obtained results indicate the selective influences of vitamin C on pro-inflammatory cytokines production in sera of lambs with pneumonic pasteurellosis and highlights the value of vitamin C as a potential anti-inflammatory drug and ideal immunomodulatory agent.


Author(s):  
Moise Ondua

Typha capensis is widely used by traditional healers to treat male fertility, venereal problems and inflammation. There are many molecular targets implicated in the inflammatory process: pro- and anti-inflammatory cytokines such as interleukin 1-β, IL-6, IL-10, IL-12p70, tumor necrosis factor alpha (TNF-α), and IL-8, and other proteins such as COX-2, and iNOS. In order to clarify the anti-inflammatory mechanism of action of compounds isolated from T. capensis, RAW 264.7 macrophages were activated by lipopolysaccharide and pre-treated with T. capensis isolated compounds. Lipopolysaccharide-stimulated RAW macrophages after treatment with T. capensis crude acetone extract resulted in decreasing expression of pro-inflammatory cytokines (TNF-α, IL-6,) and increased expression of immunomodulatory cytokine IL-12 P 70.  Isorhamnetin-3-O-β-D-glucoside and  isorhamnetin 3-O rutinoside increased the expression of pro-inflammatory cytokines TNF-α, but failed to reduce the expression of IL-1β and TNF-α. Isorhamnetin-3-O-β-D-glucoside and isorhamnetin 3-O rutinoside increased the expression of immunomodulatory cytokine IL-12p70. Isorhamnetin-3-O-β-D-glucoside  increased the expression of the anti-inflammatory cytokine IL-10 compared to quercetin and LPS-stimulated macrophages. The effect of isorhamnetin 3-O-rutinoside and isorhamnetin-3-O-β-D-glucoside on molecular targets of inflammation may provide support for the use of T. capensis by traditional healers against inflammation.


2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110556
Author(s):  
Tie Zhang ◽  
Guozhen Wang ◽  
Jing Zheng ◽  
Shirui Li ◽  
Jing Xu

Objective This study aimed to analyze the changes in serum inflammatory cytokines and anti-inflammatory cytokines in patients with gouty arthritis (GA). Methods The clinical data and serum samples in patients with gouty arthritis and those in healthy volunteers were collected in China-Japan Friendship Hospital from July 2018 to January 2019. Serum cytokine concentrations in patients with GA and volunteers (controls) were determined by a chemiluminescence method. The differences in cytokine concentrations were compared between the two groups. Results Concentrations of serum interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), IL-6, IL-8, and IL-4 were significantly higher in patients with acute GA than in controls. Serum concentrations of IL-1ß, TNF-α, IL-6, IL-8, and immunoglobulin E in patients with remission of GA were significantly lower, whereas concentrations of IL-10 and interferon-γ were significantly higher, compared with those in patients with acute GA. Conclusion This study shows that serum concentrations of IL-1ß, TNF-α, IL-6, IL-8, and IL-4 are significantly elevated in patients with GA, and may be involved in the pathogenesis of GA.


Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1238 ◽  
Author(s):  
Jonas Urich ◽  
Magali Cucchiarini ◽  
Ana Rey-Rico

Osteoarthritis (OA) is a prevalent joint disease linked to the irreversible degradation of key extracellular cartilage matrix (ECM) components (proteoglycans, type-II collagen) by proteolytic enzymes due to an impaired tissue homeostasis, with the critical involvement of OA-associated pro-inflammatory cytokines (interleukin 1 beta, i.e., IL-1β, and tumor necrosis factor alpha, i.e., TNF-α). Gene therapy provides effective means to re-establish such degraded ECM compounds by rejuvenating the altered OA phenotype of the articular chondrocytes, the unique cell population ubiquitous in the articular cartilage. In particular, overexpression of the highly specialized SOX9 transcription factor via recombinant adeno-associated viral (rAAV) vectors has been reported for its ability to readjust the metabolic balance in OA, in particular via controlled rAAV delivery using polymeric micelles as carriers to prevent a possible vector neutralization by antibodies present in the joints of patients. As little is known on the challenging effects of such naturally occurring OA-associated pro-inflammatory cytokines on such rAAV/polymeric gene transfer, we explored the capacity of polyethylene oxide (PEO) and polypropylene oxide (PPO)-based polymeric micelles to deliver a candidate rAAV-FLAG-hsox9 construct in human OA chondrocytes in the presence of IL-1β and TNF-α. We report that effective, micelle-guided rAAV sox9 overexpression enhanced the deposition of ECM components and the levels of cell survival, while advantageously reversing the deleterious effects afforded by the OA cytokines on these processes. These findings highlight the potentiality of polymeric micelles as effective rAAV controlled delivery systems to counterbalance the specific contribution of major OA-associated inflammatory cytokines, supporting the concept of using such systems for the treatment for chronic inflammatory diseases like OA.


Author(s):  
Hanie Mahaki ◽  
Naghi Jabarivasal ◽  
Khosro Sardarian ◽  
Alireza Zamani

Background: Extremely low-frequency electromagnetic fields (ELF-EMFs) are abundantly produced in modern societies. In recent years, interest in the possible effects of ELF-EMFs on the immune system has progressively increased. Objective: To examine the effects of ELF-EMFs with magnetic flux densities of 1, 100, 500, and 2000 µT on the serum levels of interleukin (IL)-9, IL-10, and tumor necrosis factor-alpha (TNF-α). Methods: 80 adult male rats were exposed to ELF-EMFs at a frequency of 50 Hz for 2 h/day for 60 days. The serum cytokines were measured at two phases of pre- and post-stimulation of the immune system by human serum albumin (HSA). Results: Serum levels of IL-9 and TNF-α, as pro-inflammatory cytokines, were decreased due to 50 Hz EMFs exposure compared with the controls in the pre- and post-stimulation phases. On the contrary, exposures to 1 and 100 µT 50 Hz EMFs increased the levels of antiinflammatory cytokine, and IL-10 only in the pre-stimulation phase. In the post-stimulation phase, the mean level of serum IL-10 was not changed in the experimental groups. Conclusion: The magnetic flux densities of 1 and 100 µT 50 Hz EMFs had more immunological effects than EMFs with higher densities. Exposure to 50 Hz EMFs may activate anti-inflammatory effects in rats, by down-modulation of pro-inflammatory cytokines (IL-9 and TNF-α) and induction of the anti-inflammatory cytokine (IL-10).


2014 ◽  
Vol 5 (4) ◽  
pp. 483-495 ◽  
Author(s):  
N. Habil ◽  
W. Abate ◽  
J. Beal ◽  
A.D. Foey

The inducible antimicrobial peptide human β-defensin-2 (hBD-2) stimulated by pro-inflammatory cytokines and bacterial products is essential to antipathogen responses of gut epithelial cells. Commensal and probiotic bacteria can augment such mucosal defences. Probiotic use in the treatment of inflammatory bowel disease, however, may have adverse effects, boosting inflammatory responses. The aim of this investigation was to determine the effect of selected probiotic strains on hBD-2 production by epithelial cells induced by pathologically relevant pro-inflammatory cytokines and the role of cytokine modulators in controlling hBD-2. Caco-2 colonic intestinal epithelial cells were pre-incubated with heat-killed probiotics, i.e. Lactobacillus casei strain Shirota (LcS) or Lactobacillus fermentum strain MS15 (LF), followed by stimulation of hBD-2 by interleukin (IL)-1β and tumour necrosis factor alpha (TNF-α) in the absence or presence of exogenous IL-10 or anti-IL-10 neutralising antibody. Cytokines and hBD-2 mRNA and protein were analysed by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. LcS augmented IL-1β-induced hBD-2, whereas LF enhanced TNF-α- and suppressed IL-1β-induced hBD-2. LF enhanced TNF-α-induced TNF-α and suppressed IL-10, whereas augmented IL-1β-induced IL-10. LcS upregulated IL-1β-induced TNF-α mRNA and suppressed IL-10. Endogenous IL-10 differentially regulated hBD-2; neutralisation of IL-10 augmented TNF-α- and suppressed IL-1β-induced hBD-2. Exogenous IL-10, however, suppressed both TNF-α- and IL-1β-induced hBD-2; LcS partially rescued suppression in TNF-α- and IL-1β-stimulation, whereas LF further suppressed IL-1β-induced hBD-2. It can be concluded that probiotic strains differentially regulate hBD-2 mRNA expression and protein secretion, modulation being dictated by inflammatory stimulus and resulting cytokine environment.


2020 ◽  
Vol 90 (1-2) ◽  
pp. 103-112 ◽  
Author(s):  
Michael J. Haas ◽  
Marilu Jurado-Flores ◽  
Ramadan Hammoud ◽  
Victoria Feng ◽  
Krista Gonzales ◽  
...  

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.


Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2794 ◽  
Author(s):  
Cao ◽  
Chen ◽  
Ren ◽  
Zhang ◽  
Tan ◽  
...  

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.


Endocrine ◽  
2021 ◽  
Author(s):  
Francesca Coperchini ◽  
Gianluca Ricci ◽  
Laura Croce ◽  
Marco Denegri ◽  
Rubina Ruggiero ◽  
...  

Abstract Introduction Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro. Purpose Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures. Methods Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants. Results The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone. Conclusions The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.


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