Increase In Levels Of IL-2 Research Articles

Characteristics of cytokine profile of wound fluid in breast cancer patients after mammoplasty with textured implants.

e12589 Background: Breast reconstruction after mastectomy for breast cancer (BC) is an important rehabilitation stage. Breast prosthesis implantation is sometimes accompanied by different complications which can be influenced by the immune system status. The aim of this study was to identify characteristics of the local cytokine profile in patients with breast cancer in the early postoperative period after reconstructive surgery with textured implants (TI). Methods: The study included 30 patients aged 32-68 years, mean age 42.9±1.98 years, with stage I-IIb BC (monocentric nodular BC, T1N0M0 - T2N1M0). All patients underwent skin-sparing mastectomy with level II axillary lymph node dissection and immediate implant reconstruction in 2017-2019. Levels of cytokines IL-1β, IL-2, IL-4, IL-6, IL-8, IFN-γ, and TNF-α were determined by ELISA in wound fluid from the cavity with TI on days 1, 3-4 and 7 after the surgery. Results: Levels of IL-6 in wound fluid of patients with TI statistically significantly decreased by 43% (p=0.036) and 41% (p=0.039) on days 3-4 and 7 after the surgery, and IL-2 decreased by 27% (p=0.045) with its further increase by 44% (p=0.037) compared to day 1. A pronounced increase of the IFN-γ levels by 118% (p=0.018) and 158% (p=0.012) was registered respectively on days 3-4 and 7 after surgery. Conclusions: Reconstructive surgery with TI is followed by a local increase in levels of IL-2 and IFN-γ which may indicate increasing antitumor potential of the microenvironment. The revealed decrease in IL-6 levels after TI implantation indicates certain features of the inflammatory reaction development in the intervention site.

Poly(Lactide-co-Glycolide) Nanoparticle-Mediated Vaccine Delivery of Encapsulated Surface Antigen Protein of Hepatitis B Virus Elicits Effective Immune Response.

Hepatitis B viral infection is one of the most important infectious diseases of the liver worldwide. Chronic infection with HBV often leads to cirrhosis and hepatocellular carcinoma. The currently licensed hepatitis B vaccine consists of recombinant hepatitis B surface antigen adsorbed into aluminum adjuvant and administered in three doses over the course of 6 months. However, this vaccine requires invasive administration and requires multiple booster doses. To avoid these limitations, nanoparticle (NP)-based vaccines lent itself as efficient adjuvants and delivery systems for the development of new generation vaccines. The biodegradable synthetic polymeric NPs poly(lactide-co-glycolide) (PLGA) was used in this study to formulate PLGA NPs encapsulated with hepatitis B surface protein to evaluate immune response in human peripheral blood lymphocytes in vitro. Formulation of HBP (HBV surface protein)-encapsulated PLGA (HB-nanovaccine [HB-NV]) was conducted by using double emulsion solvent evaporation technique (water-oil-water), which resulted in 94% encapsulation efficiency and 24% protein loading capacity. The resulted HB-NV had typical characteristics of spherical shape at an average size of 71.08 nm with higher densities and high stability dispersion of negatively charged NPs as assessed by atomic force microscopy, scanning electron microscopy, ultraviolet absorption spectrophotometry, zeta potential, and Fourier-transform infrared. The immune response to HB-NV was measured in vitro in lymphocytes, showed significant increase in levels of IL-2 and IFN-γ, as well as in CD4+ and CD8+ T cell counts, with a dose-dependent effect, examined by enzyme-linked immunosorbent assay and flow cytometry, respectively.

Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles.

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. The immune protection of the piglets derives from maternal colostrum, since this species does not receive maternal antibodies through the placenta. In the present study, outer membrane vesicles (OMVs) obtained from main ETEC strains involved in piglet infection (F4 and F18 serotypes), encapsulated into zein nanoparticles coated with Gantrez®® AN-mannosamine conjugate, were used to orally immunize mice and pregnant sows. Loaded nanoparticles were homogeneous and spherical in a shape, with a size of 220–280 nm. The diffusion of nanoparticles through porcine intestinal mucus barrier was assessed by a Multiple Particle Tracking technique, showing that these particles were able to diffuse efficiently (1.3% diffusion coefficient), validating their oral use. BALB/c mice were either orally immunized with free OMVs or encapsulated into nanoparticles (100 µg OMVs/mouse). Results indicated that a single dose of loaded nanoparticles was able to elicit higher levels of serum specific IgG1, IgG2a and IgA, as well as intestinal IgA, with respect to the free antigens. In addition, nanoparticles induced an increase in levels of IL-2, IL-4 and IFN-γ with respect to the administration of free OMVs. Orally immunized pregnant sows with the same formulation elicited colostrum-, serum- (IgG, IgA or IgM) and fecal- (IgA) specific antibodies and, what is most relevant, offspring suckling piglets presented specific IgG in serum. Further studies are needed to determine the infection protective capacity of this new oral subunit vaccine

RELATION OF Th1, Th2, Treg, Th17 CYTOKINES OF PERITONEAL FLUID IN WOMEN WITH ENDOMETRIOSIS, ASSOCIATED WITH INFERTILITY

Endometriosis is one of the leading diseases of the female reproductive organs and is the cause of almost a third of all cases of female infertility. It has been suggested that in women with endometriosis associated with infertility, the levels, nature of production and the ratio of cytokines of cells of different profiles in the peritoneal fluid change, which may play a pathogenetic role (to promote the development of immune inflammation of a certain type) in the development of the disease itself infertility.
 Aim of the study: to determine the features of the ratio of Th1, Th2, Treg, Th17 cytokines of peritoneal fluid in women with endometriosis associated with infertility.
 Materials and methods: The study group included 58 women who were diagnosed with external genital endometriosis, namely: peritoneal form and infertility for at least 2 years. The control group consisted of 30 women with tubal genital infertility. No other pathological process, at the time of observation, was detected in control patients. The study was conducted at the Center for Infertility Treatment (Chernivtsi) from 2009 to 2015, following the concept of informed consent of the patient to conduct research and other ethical principles in relation to persons who are the object of the study. Peritoneal fluid was collected during laparoscopy during the proliferative phase of the menstrual cycle. Cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA).
 The results of the study. The cytokine profile in the peritoneal fluid of women with infertility-associated endometriosis is characterized by an increase in levels of IL-2, TNF-α, IL-6, IL-17, IL-10, IL-18. The largest proportion of all cytokines under study in the peritoneal fluid is IL-10 (28%), followed by IL-2, IL-6 and IL-18 in the order of decreasing relative amount (16%, 14% and 13%, respectively). respectively. The TGF-β (7%) was then placed in relative weight reduction. TNF-α and IL-17 6% each; IL-12 (4%); IL-1β and INF-γ are 3% percent each. The lowest proportion, as in the peripheral blood, was IL-4, which was incomplete 1 percent. The total relative number of cytokines Th1 is 25%, cytokines Th2 – incomplete 15%, cytokines Treg cells – 35%, cytokines Th 17 – IL-17 is 6% and cytokines produced mainly by macrophages and killer cells – 20%. Thus, the total ratio of Th1/Th2 cytokines in women with endometriosis was 2.5:1.5.
 Conclusions: In the peritoneal fluid, pronounced changes in the cytokine profile are observed, significantly prevail over changes in the peripheral blood, and are characterized by the growth of IL-2 (p <0.001), TNF-α (p <0.001), INF-γ (p <0.001), IL -6 (p <0.001), IL-17 (p <0.001), IL-10 (p <0.001), TGF-β (p <0.05), IL-12 (p <0.001), IL-18 (p <0.001). Local production is characterized by a 2.45-fold decrease in the Th1/Th2 cytokine ratio, which indicates a predominance of the Th2-mediated immune response.

Evaluation of Preventive Effects of Brazilian Green Propolis on Equine Herpes Virus 9-Induced Acute Encephalitis

In this study, we aimed to evaluate the preventive effects of Brazilian green propolis on equine herpes virus (EHV)-induced encephalitis in a hamster model. We first investigated the antiviral activity of Brazilian green propolis against EHV-9, and then, examined the effects of propolis on the kinetics and production of cytokines. Sixtyfive male, Syrian hamsters were divided into two treatment groups and control group. The 1st group is a control. The second group was infected intranasally with 50 μl of EHV-9 [3 × 104 plaque-forming units (pfu)] without propolis treatment. The third group received propolis at 500 mg/kg of ethanol extract of Brazilian green propolis by a gavage for 7 days, followed by intranasal inoculation with 50 μl of EHV-9 (3 × 104 pfu). Pre-treatment with propolis was not effective in preventing EHV-9-induced encephalitis via intranasal route. This speculation is supported by similar clinical signs and similar immunohistochemistry based on viral antigen distribution in the brain of infected hamsters in groups 2 and 3 from 3rd day post inoculation (dpi). There were significant increases in cerebral mRNA levels of IL-2, IL-10, and IFN-𝛾 after propolis administration in the propolis-treated group before and after EHV-9 challenge compared with the control non-treated group. In conclusion, Brazilian green propolis showed no obvious effect on the prevention of acute EHV-9-induced acute encephalitis in a hamster model, despite its immune-enhancing activity.

Analysis of immunological mechanisms exerted by HBsAg-HBIG therapeutic vaccine combined with Adefovir in chronic hepatitis B patients

ABSTRACTAn HBsAg-HBIG therapeutic vaccine (Yeast-derived Immune Complexes, YIC) for chronic hepatitis B (CHB) patients has undergone a series of clinical trials. The HBeAg sero-conversion rate of YIC varied from 21.9% to 14% depending on the immunization protocols from 6 to 12 injections. To analyze the immunological mechanisms exerted by 6 injections of YIC, 44 CHB patients were separately immunized with YIC, alum as adjuvant control or normal saline as blank control, with add on of antiviral drug Adefovir in all groups. Kinetic increase in Th1 and Th2 cells CD4+ T cell sub-populations with association in decrease in Treg cells and increase of Tc1 and Tc17 cells in CD8+ T cells were observed in YIC immunized group. No such changes were found in the other groups. By multifunctional analysis of cytokine profiles, significant increase of IL-2 levels was observed, both in CD4+ and CD8+ T cells in the YIC immunized group, accompanied by increase in IFN-gamma and decrease of inhibitory factors (IL-10, TGF-β and Foxp3) in CD4+ T cells. In the alum immunized group, slight increase of IL-10, TGF-β and Foxp3 in CD4+ T cells was found after the second injection, but decreased after more injections, suggesting that alum induced early inflammatory responses to a certain extent. Similar patterns of responses of IL-17A and TNF-α in CD8+T cells were shown between YIC and the saline group. Results indicate that add on of Adefovir, did not affect host specific immune responses.

Factors affecting T cell responses induced by fully synthetic glyco-gold-nanoparticles

We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono- and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines.

Acute resistance exercise results in catecholaminergic rather than hypothalamic–pituitary–adrenal axis stimulation during exercise in young men

Exercise is a paradigm of a stress situation. The adaptive response to stressors comprises the activation of the hypothalamic–pituitary–adrenal (HPA) axis and components of the autonomic sympathetic system. An aseptic inflammatory reaction is triggered by exercise, involving the stimulation of the so-called proinflammatory cytokines, such as tumor necrosis factor α (TNFα), interleukin-1 (IL-1), and IL-6. The anti-inflammatory cytokines IL-2, IL-8, and IL-10 increase moderately during resistance exercise. To investigate the effect of a short bout of resistance exercise on components of the stress and inflammatory responses during the exercise period, 17 healthy, young, untrained male volunteers were studied during 3 equal consecutive cycles of resistance exercises of 30 min total duration. Blood sampling was performed at baseline and at the end of each cycle. Lactate, cortisol, catecholamines (epinephrine, norepinephrine), IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, epidermal growth factor (EGF), and monocyte chemotactic protein-1 (MCP-1) were measured at all time-points. Circulating levels of catecholamines and lactate increased significantly (P < 0.05) whereas cortisol did not. During the time course of the exercise, circulating levels of TNFα, IL-2, and EGF increased, whereas MCP-1 decreased significantly. IL-1α, IL-1β, IL-6, IL-8, and IL-10 levels did not change significantly. Statistically significant positive linear correlations were found between areas under the curve for increases in levels of IL-2 and TNFα, TNFα and cortisol, as well as epinephrine and norepinephrine. We conclude that acute resistance exercise results in catecholaminergic, but not HPA axis stimulation during exercise, in parallel with a mild inflammatory reaction. The absence of a major inflammatory reaction and of a cortisol increase during acute resistance exercise makes this a good candidate for the exercise of sedentary individuals.

Predictive utility of serum cytokine levels in patients with metastatic renal cell carcinoma (MRCC) treated with interferon alfa (IFNa)

14503 Background: IFNa may prolong survival in MRCC patients (pts) due to stimulation of cell-mediated immunity. We hypothesized that IFNa exerts an anti-tumor effect by upregulation of Th1 cytokines and that patients (pts) with elevated serum levels of Th1 cytokines either at baseline (BL) or after treatment with IFNa would have a superior clinical outcome. Methods: Cytokine profiling was performed on 104 pts with MRCC treated in a randomized phase III trial with IFNa 0.5 million units (MU) subcutaneously (SC) twice daily or 5 MU SC daily. Serum samples were collected at BL (n = 104) and after 8 weeks of IFNa therapy (C1) (n = 89). Cytokine concentrations were determined using a 16-plex immunoassay. The linear mixed-effect model was fit to assess the change of cytokine levels from BL to C1. Cox proportional hazards model was fit to evaluate the effect of BL cytokine levels or change of cytokine levels from BL to C1 on the risk of death. Results: Of 16 cytokines evaluated (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFNa, IFNg, GM-CSF, TNFa, VEGF), lower BL TNFa, IL-8 (Th1), and IL-13 (Th2) levels were associated with clinical benefit (major response or progression-free status at 6 months) (p = 0.01 and 0.03, respectively). By multivariate analysis, only extremely low or high levels of IFNa (p = 0.02) and IL-12 (p = 0.002) at BL were associated with an increased risk of death. IFNa therapy after C1 produced higher levels of several Th1 cytokines (IL-8, IL-12 p40, IL-15) (p &lt; .001) and lower levels of Th2 cytokines (IL-4, IL-13). Unexpectedly, there were significantly lower levels of TNFa and GM-CSF (Th1) and higher levels of IL-10 (Th2) with IFNa. Only an increase of IL-2 levels from BL to C1 (RR 1.45; p = 0.05) correlated with an increased risk of death. Conclusions: Lower BL serum levels of TNFa, IL-8, and IL-13 were associated with clinical benefit to IFNa. Although IFNa therapy favored a shift towards a Th1 response, this effect alone did not correlate with clinical outcome. No significant financial relationships to disclose.

Inhibition of graft-versus-host disease by interleukin-2 treatment is associated with altered cytokine production by expanded graft-versus-host-reactive CD4+ helper cells.

In a fully MHC plus multiple minor antigen-mismatched murine bone marrow transplantation (BMT) model, we have demonstrated that a short course of high dose IL-2, begun on the day of BMT, protects against graft-versus-host disease (GVHD). This inhibitory effect is directed against donor CD4+ cells. To determine whether the mechanism of IL-2-induced GVHD protection involves clonal deletion or anergy of host-reactive donor T helper cells (Th), we performed limiting dilution analyses to measure the frequency of activated Th that reacted to donor, host, and third-party antigens in GVHD control and IL-2-protected mice. Marked and specific expansion of host-reactive Th was observed to a similar extent in GVHD control and IL-2-protected mice by day 5 after BMT, and the number of these cells in the spleen increased by several orders of magnitude between days 3 and 5 after BMT, which suggests that recirculation from other tissues occurred in this period. A high proportion (approximately 80%) of donor T cells expressed CD25 in both GVHD control and IL-2-protected mice on day 4 after BMT, which suggests a high level of bystander T cell activation. Since marked quantitative differences in the GVH response were not observed between GVHD control and IL-2-protected mice, we assessed both groups for qualitative differences in the Th response. Spleen cells isolated in the first 8 days after BMT were cultured with host-type, donor-type, or third-party stimulators or without stimulators, and cytokines were measured in supernatants harvested at 24 hr. GVHD was associated with marked increases in supernatant IFN-gamma levels from day 3 to day 6 after BMT, and with increases in IL-2 levels compared with naive A/J controls or syngeneic BMT controls stimulated with host antigens. Production of these cytokines was specifically induced by host-type antigens. Supernatants from spleens of IL-2-treated mice showed delayed kinetics of IFN-gamma production, and tended to contain higher levels of IL-4 in response to host antigen compared with GVHD controls on days 2 and 4 after BMT. Both IL-4 and IFN-gamma were produced almost exclusively by CD4+ cells in spleens of GVHD control and IL-2-protected mice on day 4. However, no consistent difference was observed between the groups in supernatant IL-2 or IL-10 levels, ruling out a simple Th1 to Th2 switch.(ABSTRACT TRUNCATED AT 400 WORDS)