Effects of Interferon Beta, Cyclophosphamide and Azathioprine on Cytokine Profile in Patients with Multiple Sclerosis

2005 ◽  
Vol 18 (2) ◽  
pp. 377-383 ◽  
Author(s):  
R. Totaro ◽  
A. Passacantando ◽  
T. Russo ◽  
I. Parzanese ◽  
M. Rascente ◽  
...  

We assessed the in vitro effects of interferon beta-1b (IFNβ-1b), cyclophosphamide (CY), and azathioprine (AZA) alone and of the combination of IFNβ-1b with CY or AZA on the production of Th1 and Th2 cytokines in 10 patients with multiple sclerosis. Cytokine levels were determined at baseline and after stimulation with IFNβ-1b, CY, and AZA alone or with the combination of IFNβ-1b with CY or AZA. The combination of IFNβ-1b with CY resulted in a statistically significant decrease in the production of interleukin-2 (IL-2) (P=0.003) and tumor necrosis factor alfa (TNF-α) (P=0.03). An additive effect on the production of interferon gamma (IFN-γ) (P=0.2) and interleukin-10 (IL-10) (P=0.6), and a positive interaction on the production of interleukin-4 (IL-4) (P=0.08) were observed although the findings were not statistically significant. The combination of IFNβ-1b with AZA resulted in a significant negative effect on the production of IL-2 (P=0.006), whereas TNF-α (P=0.02), IFN-γ (P=0.03), IL-4 (P=0.2), and IL-10 (P=0.3) were not statistically impacted. Our data show that CY was able to improve the effects of IFNβ-1b on the ratio of Th1/Th2 cytokines.

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.


1997 ◽  
Vol 56 ◽  
pp. 465
Author(s):  
A. Gayo ◽  
L. Mozo ◽  
A. Suárez ◽  
A. Tuñón ◽  
C. Lahoz ◽  
...  

2000 ◽  
pp. 31-36 ◽  
Author(s):  
JA Giron-Gonzalez ◽  
FJ Moral ◽  
J Elvira ◽  
D Garcia-Gil ◽  
F Guerrero ◽  
...  

OBJECTIVE: To evaluate the T helper 1 (T(H)1)/T helper 2 (T(H)2) lymphocyte cytokine profiles in women and men and to study the in vitro effects of sex hormones on lymphocyte secretion of cytokines. METHODS: Analysis of serum concentration and lymphocyte synthesis of T(H)1 (gamma interferon (INF-gamma) and interleukin 2 (IL-2)) and T(H)2 (interleukin 4 (IL-4) and interleukin 10 (IL-10)) cytokines was performed in 20 women and 15 men. Analysis of modifications in cytokine secretion induced by supplementation of lymphocyte culture with increasing concentrations of sex hormones was carried out. RESULTS: Higher levels of INF-gamma and IL-2 and lower levels of IL-4 and IL-10 were detected in the phytohemagglutinin-stimulated lymphocyte culture supernatants of men compared with women; the INF-gamma:IL-4 ratio was significantly higher in men. In women, similar concentrations of all the cytokines were detected in culture supernatants obtained during the follicular and the luteal phases. The addition of sex hormones did not modify the concentration of cytokines in supernatants of phytohemagglutinin-stimulated T-cell cultures. CONCLUSIONS: Women present a predominant T(H)2 cytokine profile, which could be involved in immune responses characterized principally by the secretion of antibodies. This could be a factor implicated in the higher concentration of immunoglobulins or the increased prevalence of autoimmune diseases detected in females.


1996 ◽  
Vol 98 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Jan Philippé ◽  
Jan Debruyne ◽  
Geert Leroux-Roels ◽  
Annick Willems ◽  
Jacques Dereuck
Keyword(s):  
Tnf Α ◽  

2006 ◽  
Vol 82 (4) ◽  
pp. 501-507 ◽  
Author(s):  
S.L. Yuan ◽  
X.S. Piao ◽  
D.F. Li ◽  
S.W. Kim ◽  
H.S. Lee ◽  
...  

AbstractAn experiment was conducted to evaluate the effects of dietary supplementation of a polysaccharide isolated from Astragalus membranaceus (APS) on performance and immune responses in weaned pigs. A total of 144 crossbred pigs weaned at 26 to 30 days of age with an average initial live weight (LW) of 7·64 (s.d. 0·290) kg were randomly allotted to six diets supplemented with APS at 0, 100, 250, 500, 750, and 1000 mg/kg. There were six replicates (three barrow pens and three gilt pens) per diet treatment with four pigs per pen. Pigs were given food ad libitum for 21 days and the LW and food intake were measured on days 14 and 21. Pigs were intramuscularly injected with 1 mg/kg LW ovalbumin (OVA) on day 14 to evaluate humoral immune response. Blood samples were collected on day 21 to measure leukocyte differential counts, percentage of blood CD4+ and CD8+ lymphocyte subsets, lymphocyte proliferation response to Concanavalin A, serum concentration of immunoglobulin G (Ig G), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-γ (IFN-γ) and specific OVA antibody. The results showed that the average daily gain, the numbers of WBC and lymphocytes, the proportion of CD4+ lymphocyte subset, and the contents of IL-2 and IFN-γ increased ( P < 0·05) as pigs were fed increased supplemental level of APS during the 21 d period. However, the contents of specific OVA antibody, Ig G, IL-4, and IL-10 were not affected ( P > 0·05) by dietary levels of APS. The broken line analysis and quadratic regression analysis indicate that the optimal APS supplemental level would be between 381 mg/kg and 568 mg/kg for the maximal ADG and from 324 to 563 mg/kg for immune responses. Collectively, this study suggests that dietary APS can be used as a potential immuno-modulating agent by affecting cellular immunity of weaned pigs.


2001 ◽  
Vol 69 (2) ◽  
pp. 687-694 ◽  
Author(s):  
Isabel Diterich ◽  
Luc Härter ◽  
Dieter Hassler ◽  
Albrecht Wendel ◽  
Thomas Hartung

ABSTRACT In lipopolysaccharide-stimulated blood from 71 late-stage borreliosis patients, the ex vivo cytokine release capacity of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) was reduced to 28% ± 5% and to 31% ± 5% (P ≤ 0.001), respectively, compared to that of 24 healthy controls. White blood cell counts were normal in both groups. To investigate direct interactions between the pathogen and the immune cells, blood from healthy controls was exposed in vitro to live or heat-killedBorrelia or to Borrelia lysate. Compared to the pattern induced by bacterial endotoxins, a reduced release of TNF-α and IFN-γ and an enhanced secretion of interleukin-10 and granulocyte colony-stimulating factor was found. In blood from 10 borreliosis patients stimulated with Borrelia lysate, TNF-α formation was decreased to 31% ± 14% and IFN-γ formation was decreased to 8% ± 3% (P ≤ 0.001) compared to the cytokine response of blood from healthy controls (n = 24). We propose to consider anti-inflammatory changes in the blood cytokine response capacity elicited by Borrelia as a condition that might favor the persistence of the spirochete.


2007 ◽  
Vol 75 (8) ◽  
pp. 4006-4011 ◽  
Author(s):  
Dhammika H. M. L. P. Navarathna ◽  
Kenneth W. Nickerson ◽  
Gerald E. Duhamel ◽  
Thomas R. Jerrels ◽  
Thomas M. Petro

ABSTRACT Candida albicans, a dimorphic fungus composed of yeast and mycelial forms, is the most common human fungal pathogen. Th1 cytokines such as interleukin-2 (IL-2), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), which are induced by macrophage IL-12, are critical to resistance against systemic candidiasis, while Th2 cytokines such as IL-4 and IL-5 are less critical. Farnesol is a quorum-sensing molecule produced by C. albicans that controls the formation of mycelia but is also a virulence factor. To determine whether farnesol enhances the virulence of C. albicans by modulating the production of Th1 and Th2 cytokines, mice were pretreated with farnesol prior to intravenous infection with a sublethal dose of farnesol-producing C. albicans. Production of IL-2, IL-4, IL-5, TNF-α, IFN-γ, and IL-12 was evaluated by bead-array flow cytometry and enzyme-linked immunosorbent assay. Mice exhibited an elevation in serum TNF-α levels at 48 h and an elevation in IFN-γ and IL-12 levels at 6 to 12 h after infection with C. albicans. Pretreatment with farnesol significantly reduced the elevation of both IFN-γ and IL-12 but not TNF-α. In contrast, mice pretreated with farnesol exhibited an unexpected elevation in IL-5 levels. To determine whether farnesol has a direct effect on macrophage production of IL-12, peritoneal macrophages were pretreated with farnesol prior to stimulation with IFN-γ plus lipopolysaccharide (LPS). Farnesol inhibited production of both IL-12 p40 and p70 from IFN-γ/LPS-stimulated macrophages. Therefore, the role of farnesol in systemic candidiasis is likely due to its ability to inhibit the critical Th1 cytokines IFN-γ and IL-12 and perhaps to enhance a Th2 cytokine, IL-5.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.


Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1230
Author(s):  
Sumin Pyeon ◽  
Ok-Kyung Kim ◽  
Ho-Geun Yoon ◽  
Shintae Kim ◽  
Kyung-Chul Choi ◽  
...  

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by immune hypersensitivity reaction. The cause of AD is unclear, but its symptoms have a negative effect on quality of life; various treatment methods to alleviate these symptoms are underway. In the present study, we aimed to evaluate in vitro antioxidant and anti-inflammatory effects of Rubus coreanus water extract (RCW) on AD. Total phenolic compounds and flavonoid content of RCW were 4242.40 ± 54.84 mg GAE/g RCE and 1010.99 ± 14.75 mg CE/g RCW, respectively. RCW reduced intracellular reactive oxygen species level and increased the action of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase in tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-stimulated HaCaT cells. Moreover, mRNA expression of the pro-inflammatory cytokines, including TNF-α, interleukin-1β, and interleukin-6, was downregulated by RCW in the TNF-α/IFN-γ-stimulated cells. The levels of inflammatory chemokines (thymus- and activation-regulated chemokine; eotaxin; macrophage-derived chemokine; regulated on activation, normal T-cell expressed and secreted; and granulocyte-macrophage colony-stimulating factor) and intercellular adhesion molecule-1 were decreased in the TNF-α/IFN-γ-stimulated HaCaT cells after RCW treatment. Additionally, the mRNA expression levels of filaggrin and involucrin, proteins that form the skin, were increased by RCW. Furthermore, RCW inhibited the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway in the TNF-α/IFN-γ-stimulated HaCaT cells. Collectively, the present investigation indicates that RCW is a potent substance that inhibits AD.


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