scholarly journals Nintedanib reduces corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice by increasing the expression of β3 & β6 integrins

Author(s):  
doha omar alghamdi ◽  
Hala S Abdel Kawy ◽  
zuhair A Damanhouri

Abstract Background: Corticosteroid resistance pulmonary fibrosis is a major health problem. This study aimed to determine the effectiveness of nintedanib on corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice. Methods: The mice were divided into five groups 12 mice each. control group, BLM group received single dose of bleomycin (BLM), BLM+MP group received BLM and methylprednisolone (MP), BLM+NIN group received BLM and nintedanib(NIN) and BLM + NIN + MP group. The lung tissues were obtained for biochemical analysis, gene expression and histopathological examination on day 7 and day 28. Results: after 7 days, both NIN groups showed a significant decrease in the levels of interleukin-2, interleukin-4, interferon-gamma, lung tumor necrosis factor-alpha, Malondialdehyde and lung water content with a significant increase in the Glutathione level in lung tissues compared to MP group. After 28 days, both NIN groups showed a significant reduction in hydroxyproline, and Trans-forming Growth Factor beta lung tissues contents compared to MP group, and they showed a positive effect on the expression of β 3 &β6 integrins compared to the negative effect of MP group. Histopathologically, both NIN groups showed significant improvement compared to MP group by H&E and Masson’s trichrome stains. Immunohistochemical staining revealed negative BCL-2 expression in the cytoplasm of bronchiolar epithelium in both NIN groups after 7 and 28 days of treatment. Lung tissue morphometric studies showed significant improvement of pathological changes induced by BLM in both NIN groups. Conclusions: Altogether, our data indicates that nintedanib overcame corticosteroid resistance pulmonary fibrosis induced by bleomycin.

2021 ◽  
Author(s):  
Doha O Alghamdi ◽  
Hala S Abdel Kawy ◽  
Zuhair A Damanhouri

Abstract Background:Corticosteroid resistance pulmonary fibrosis is a major health problem. This study aimed to determine the effectiveness of nintedanib on corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice.Methods:The mice were divided into five groups 12 mice each. control group, BLM group received single dose of bleomycin (BLM), BLM+MP group received BLM and methylprednisolone (MP), BLM+NIN group received BLM and nintedanib(NIN) and BLM + NIN + MP group. The lung tissues were obtained for biochemical analysis, gene expression and histopathological examination on day 7 and day 28.Results:After 7 days, both NIN groups showed a significant decrease in the levels of interleukin-2, interleukin-4, interferon-gamma, lung tumor necrosis factor-alpha, Malondialdehyde and lung water content with a significant increase in the Glutathione level in lung tissues compared to MP group. After 28 days, both NIN groups showed a significant reduction in hydroxyproline, and Trans-forming Growth Factor beta lung tissues contents compared to MP group, and they showed a positive effect on the expression of β 3 &β6 integrins compared to the negative effect of MP group. Histopathologically, both NIN groups showed significant improvement compared to MP group by H&E and Masson’s trichrome stains. Immunohistochemical staining revealed negative BCL-2 expression in the cytoplasm of bronchiolar epithelium in both NIN groups after 7 and 28 days of treatment. Lung tissue morphometric studies showed significant improvement of pathological changes induced by BLM in both NIN groups.Conclusion:Altogether, our data indicates that nintedanib overcame corticosteroid resistance pulmonary fibrosis induced by bleomycin.


2021 ◽  
Author(s):  
doha omar alghamdi ◽  
Hala S Abdel kawy ◽  
Zhair A Damanhouri

Abstract Background: Corticosteroid resistance pulmonary fibrosis is a major health problem. This study aimed to determine the effectiveness of nintedanib on corticosteroid resistance pulmonary fibrosis induced by bleomycin in mice. Methods: The mice were divided into five groups 12 mice each. control group, BLM group received single dose of bleomycin (BLM), BLM+MP group received BLM and methylprednisolone (MP), BLM+NIN group received BLM and nintedanib(NIN) and BLM + NIN + MP group. The lung tissues were obtained for biochemical analysis, gene expression and histopathological examination on day 7 and day 28. Results: after 7 days, both NIN groups showed a significant decrease in the levels of interleukin-2, interleukin-4, interferon-gamma, lung tumor necrosis factor-alpha, Malondialdehyde and lung water content with a significant increase in the Glutathione level in lung tissues compared to MP group. After 28 days, both NIN groups showed a significant reduction in hydroxyproline, and Trans-forming Growth Factor beta lung tissues contents compared to MP group, and they showed a positive effect on the expression of β 3 &β6 integrins compared to the negative effect of MP group. Histopathologically, both NIN groups showed significant improvement compared to MP group by H&E and Masson’s trichrome stains. Immunohistochemical staining revealed negative BCL-2 expression in the cytoplasm of bronchiolar epithelium in both NIN groups after 7 and 28 days of treatment. Lung tissue morphometric studies showed significant improvement of pathological changes induced by BLM in both NIN groups. Conclusion: Altogether, our data indicates that nintedanib overcame corticosteroid resistance pulmonary fibrosis induced by bleomycin.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Seul-Ki Kim ◽  
Da-Ae Kwon ◽  
Hak Sung Lee ◽  
Hyun Kyu Kim ◽  
Won-Ki Kim

We determined the functional effect of the herbal preparation, HemoHIM, on the immune system, by examining the immunomodulatory activities of HemoHIM using immunocompromised mice. In this study, to examine the effect on the restoration of immune cells and balance in the immune system, we utilized a cisplatin-induced immunosuppression mouse model. Mice were injected intraperitoneally with cisplatin, an immunosuppressive anticancer, and then received oral doses of 100, 250, and 500 mg/kg of HemoHIM for 14 days. The HemoHIM prevented the cisplatin-induced loss of body and organ weight. In terms of innate immunity, natural killer (NK) cell activity and phagocytosis increased in the HemoHIM group compared to the cisplatin control group. The HemoHIM group also showed a significantly higher expression of Th1-mediated cytokines (interferon gamma (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor alpha (TNF-α)) and inhibited the production of Th2-mediated cytokine interleukin-4 (IL-4) compared to cisplatin control group. These findings indicate that HemoHIM enhances immune activity by modulating immune cell activity and cytokine secretion in immune-suppressed mice.


2019 ◽  
Vol 17 ◽  
pp. 205873921881868
Author(s):  
Limei Liu ◽  
Dongdong Wei ◽  
Hongkun Xu ◽  
Changhui Liu

To study the effects of apigenin on dry eye disease (DED) in rats. Rats were divided into six groups: (I) normal control group, (II) DED control group, (III) vehicle control group, (IV) DED + apigenin 10 mg/kg, (V) DED + apigenin 20 mg/kg, and (VI) DED + apigenin 50 mg/kg. Schirmer test, tear film break-up time (BUT), and corneal fluorescein staining were used to evaluate the effects of apigenin on the ocular surface. The related inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). Histopathological examination and inflammatory index were also performed. The results showed that administration of apigenin was shown a significant effect on the recovery of ocular surface function. Compared to the control group, apigenin treatment in DED rats significantly decreased the level of the tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6); however, the interleukin-10 (IL-10) level was increased. Histopathological examination further verified the anti-inflammatory effects of apigenin on DED rats. The results demonstrated that apigenin could protect DED rats via inhibition of inflammation, suggesting that it may have potential as a therapy for DED.


2014 ◽  
Vol 95 (5) ◽  
pp. 642-645
Author(s):  
O V Skidanenko-Levina

Aim. To study the levels of pro- and anti-inflammatory cytokines in cervical secretion in females with cervical epithelial dysplasia and latent papillomavirus infection. Methods. The study included 120 females aged 20 to 40 years with cervical papillomavirus infection, who were assigned to two groups using «case-control» method. The first group included 60 females with latent disease, the second group - 60 females with mild and moderate cervical epithelial dysplasia (cervical intraepithelial neoplasia stages I and II). Cytokine levels in cervical secretion were measured by ELISA using «ProCon» test system. Results. ELISA test showed increased levels of interleukin-4 and interleukin-10 (43 [21; 74] and 48 [12; 88] pg/ml, respectively) and decreased levels of interleukin-2 (18.5 [5.5; 27.5] pg/ml), interleukin-6 (0.6 [0.06; 0.9] pg/ml), tumor necrosis factor alpha (88.5 [0; 123] pg/ml), interferon γ (2 [0; 4] pg/ml) in cervical secretion of females with cervical epithelial dysplasia compared to females with latent papillomavirus infection. Thus, females with cervical epithelial dysplasia showed increased levels of anti-inflammatory cytokines: interleukin-4 - by 2.7 times and interleukin-10 - by 2.4 times compared to females with latent disease, while levels of pro-inflammatory cytokines was decreased as following: interleukin-2 - by 1.4 times, interleukin-6 - by 4.5 times, tumor necrosis factor alpha - by 1.8 times, interferon γ - by 6.3 times (p 0.05). Conclusion. Imbalance of immune response cytokine regulation with anti-inflammatory cytokines prevailing might be an important factor facilitating persistence of papillomavirus in cervical epithelium and contributing to cervical epithelial dysplasia onset and progression.


Lupus ◽  
1993 ◽  
Vol 2 (1_suppl) ◽  
pp. 257-260 ◽  
Author(s):  
Maria J. Cuadrado ◽  
Miriam Marubayashi ◽  
Consuelo Ortega ◽  
Nieves Fernandez-Arcas ◽  
Francisco Garcia-Cozar ◽  
...  

The plasma levels of interleukin-4 (IL-4), interleukin-2 (IL-2), soluble receptor of IL-2 (IL-2R) and T cell expression of IL-2 receptor chain (CD25+) were determined in an attempt to relate these parameters with disease activity in systemic lupus erythematosus (SLE). IL-4, IL-2 and sIL-2R plasma levels of SLE patients were significantly higher than those of the control group (P<0.05) while CD25+ expression was similar in both groups. Only sIL-2R levels were significantly higher (P<0.05) in active than in inactive patients.


Author(s):  
Hong Wang ◽  
◽  
Chen-Yu Chen ◽  
Yong Zhu ◽  
Ji-Pu Zhou ◽  
...  

To investigate effectsof Yangyinyiqi Mixture on pulmonary fibrosis caused by bleomycin. SD ratswere divided randomly into: model group(distilled water,1 mL·0.1 kg-1), dexamethasone acetate group(dexamethasone acetate, the dosage was reduced gradually), low-dose group(Yangyinyiqi Mixture, 11 g·kg-1), moderate-dose group(Yangyinyiqi Mixture, 22 g·kg-1), high-dose group (Yangyinyiqi Mixture, 44 g·kg-1) and control group(distilled water, 1 mL·0.1 kg-1). Yangyinyiqi Mixture and dexamethasone acetate were intragastrically administrated. Lung tissue was collected for histopathological examination. Compared with control group, collagen markedly increased andHYP content significantly increased on 7th day in model group (p<0.01). On 28th day, collagen was diffusely deposited, alveolar was destroyed, and HYP content significantly increased (p<0.01). Compared with model group, bleomycin-induced suffering injury caused MMP-9 expression levels to rapidly increase (7and 14 days, p<0.01). TIMP-1 markedly increased (7and 14 days, p<0.01) and stayed at a high levelto28th day. Yangyinyiqi Mixture exerted an effect against pulmonary fibrosis, which could involved prevention of collagen deposition through inhibitingMMP-9 and TIMP-1 expression.


2021 ◽  
Vol 8 ◽  
Author(s):  
Elena Navarro ◽  
Eva Mainau ◽  
Ricardo de Miguel ◽  
Déborah Temple ◽  
Marina Salas ◽  
...  

Many factors can lead to an inadequate development of piglets during their first days of life, including poor maternal behavior, which can be due to pain caused by farrowing, and reduced colostrum ingestion. This study investigates the action of meloxicam administered orally at farrowing on piglet weight gain and immunity transfer. Thirty-five multiparous sows were divided into two groups and treated with 0.4 mg/kg of oral meloxicam (oral meloxicam group; n = 18) or with a mock administration (control group; n = 17). A total of 382 piglets were individually weighed on the farrowing day (day 0), as well as on days +9 and +20. Immunoglobulin G (IgG) and A (IgA) concentrations in piglet serum and in sow's saliva, colostrum and milk were measured. Additionally, Interleukin-2 (IL-2), Interleukin-4 (IL-4) and Interferon gamma (IFN-⋎) in serum of piglets and in sow's milk or colostrum were studied. All samples were obtained on days +1, +9, and +20. Piglets from sows in the oral meloxicam group tended to grow faster from day +9 to day +20 than did piglets from control sows (p = 0.059), and this difference was also observed in piglets with low body weight (BW) at birth (p = 0.056). The oral meloxicam group sows tended to increase the colostrum levels of IgA and IgG, as compared with control sows on day +1 (p = 0.068 and p = 0.072, respectively). IgA levels in piglet serum from the oral meloxicam group were significantly higher than in the control group on day +1 and +9 (p = 0.019 and p = 0.011 respectively). Furthermore, IL-2 and IL-4 levels in the serum of piglets from sows in the oral meloxicam group tended to be higher than that in the control group on day +9 (p = 0.078 and 0.056, respectively). The administration of meloxicam orally at the beginning of farrowing in multiparous sows increased immunoglobin and cytokine concentrations in colostrum, improving both humoral and cellular immune response of piglets. Pre-weaning growth of piglets born with a low BW improved in the meloxicam-treated group.


2013 ◽  
Vol 59 (1) ◽  
pp. 31-35
Author(s):  
Zsuzsánna Réti ◽  
Iz Kun ◽  
Corina Cristina Radu Pop

Abstract Background: Graves’ orbitopathy (GO) is considered an autoimmune condition in close relationship with Graves’ disease (GD) affecting the thyroid. Several similarities exist between the two conditions, sharing the common antigen and the characteristics of the inflammation mediated by a number of cytokines. The result of the immune reactions will lead to the expansion of adipose tissue, production of glycosaminoglycans and soft tissue inflammation. Material and methods: In our study we examined the serum level of interleukin-1 (IL-1), interleukin 2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) in correlation with the activity of disease and smoking habits in 25 patients with GD and GO. Results: We found that smokers had higher serum IL-6 and lower serum MCP-1, IL-8 and TNF-α level compared to non-smokers. Also, we found a weak positive correlation between serum IL-10, IFN-γ and disease activity (clinical activity score, CAS) and negative correlation between serum IL-1 and activity. Conclusion: Our findings support the fact that some cytokines (IL-10, IFN-γ, IL-1) play a role in active disease, while others are influenced by environmental factors, such as smoking (IL-6, IL-8, TNF-α). The discrepancy of cytokine profiles may reflect different patient characteristics, such as disease stage and disease activity and determination of serum cytokines would be useful in selecting patients who need more aggressive treatment protocols.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 263-263
Author(s):  
Sergey Shabunin ◽  
Vitaly Mikhalev

Abstract The aim of the study was to research the cytokine profile of cow blood in the treatment of acute postpartum endometritis with the use of recombinant α-, γ-interferons. Animals of the first group (n = 9) with a diagnosis of acute postpartum endometritis were intramuscularly injected with propranolol hydrochloride, denatured emulsified placenta, and nioxityl. Propranolol hydrochloride was administered for 4 days at a dose of 10 ml/animal at 24-hour intervals. The denatured emulsified placenta was injected subcutaneously on days 1-5-9 at a dose of 25 ml /animal. Nioxityl was injected intrauterine at a dose of 150 ml three times with a 48-hour interval. Cows of the second group (n = 11) with the same diagnosis were additionally injected intramuscularly with bovine recombinant α-, γ-interferons three times in 1–3 days at a dose of 5 ml/animal, 1 cm3 of which contains at least 1x104 IU/cm3 of the total antiviral activity of bovine recombinant α-, γ-interferons. Blood samples are taken from all groups before and at the end of the experiment. Blood samples are examined for the content of interleukin-2 (IL-2), interleukin-4 (IL-4), tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10) using Bovine Elisa Kit Clood-Clone Corp (USA). The therapeutic effectiveness in the first group was 77.8%, in the second - 90.9%, which is 13.1% more. At the end of the course, the level of IL-2 decreased by 42.5% (43.5±4.2 pg/ml, P &lt; 0.01), TNF-Α by 9.1% (457.9±34.6 pg/ml), the level of IL-4 increased by 14.8% (44.2±3.5 pg/ml, P &lt; 0.05), IL-10 by 56.6% (35.7±2.8 pg/ml, P &lt; 0.01). In the second group, the level of anti-inflammatory cytokines decreased: IL–2 by 48.7% (38.8±1.6 pg/ml, P &lt; 0.01), TNFα by 26% (372.5±17.6 pg/ml, P &lt; 0.05) and increased anti–inflammatory cytokines: IL-4 by 46.2% (56.3±4.1 pg/ml, P &lt; 0.001) and IL-10 by 80.3% (41.1±3.5 pg/ml, P &lt; 0.001), which indicates a decrease in the inflammatory response.


Sign in / Sign up

Export Citation Format

Share Document