scholarly journals Effects of Interleukin-4 Deprivation and Treatment on Resistance to Trypanosoma cruzi

2000 ◽  
Vol 68 (4) ◽  
pp. 1975-1979 ◽  
Author(s):  
Ises A. Abrahamsohn ◽  
Ana Paula Galvão da Silva ◽  
Robert L. Coffman
Keyword(s):  
Monoclonal Antibodies ◽  
Trypanosoma Cruzi ◽  
Concanavalin A ◽  
Mortality Rates ◽  
Interleukin 4 ◽  
Wild Type ◽  
Spleen Cells ◽  
Parasite Antigen ◽  
Significant Difference ◽  
Ifn Γ

ABSTRACT Trypanosoma cruzi (Y strain)-infected interleukin-4−/− (IL-4−/−) mice of strains 129/J, BALB/c, and C57BL/6 showed no significant difference in parasitemia levels or end point mortality rates compared to wild-type (WT) mice. Higher production of gamma interferon (IFN-γ) by parasite antigen (Ag)-stimulated splenocytes was observed only for C57BL/6 IL-4−/− mice. Treatment of 129/J WT mice with recombinant IL-4 (rIL-4), rIL-10, anti-IL-4, and/or anti-IL-10 monoclonal antibodies (MAbs) did not modify parasitism. However, WT mice treated with rIL-4 and rIL-10 had markedly increased parasitism and suppressed IFN-γ synthesis by spleen cells stimulated with parasite Ag, concanavalin A, or anti-CD3. Addition of anti-IL-4 MAbs to splenocyte cultures from infected WT 129/J, BALB/c, or C57BL/6 mice failed to modify IFN-γ synthesis levels; in contrast, IL-10 neutralization increased IFN-γ production and addition of rIL-4 and/or rIL-10 diminished IFN-γ synthesis. We conclude that endogenous IL-4 is not a major determinant of susceptibility to Y strain T. cruziinfection but that IL-4 can, in association with IL-10, modulate IFN-γ production and resistance.

scholarly journals In Vivo Expression of and Cell-Mediated Immune Responses to the Plasmid-Encoded Virulence-Associated Proteins of Rhodococcus equi in Foals

2007 ◽  
Vol 14 (4) ◽  
pp. 369-374 ◽  
Author(s):  
Stephanie Jacks ◽  
Steeve Giguère ◽  
John F. Prescott
Keyword(s):  
Lymph Node ◽  
Rhodococcus Equi ◽  
Interleukin 4 ◽  
Significant Difference ◽  
In Vivo Expression ◽  
Associated Proteins ◽  
Ifn Γ ◽  
Bronchial Lymph Node

ABSTRACT Rhodococcus equi is a facultative intracellular pathogen that causes pneumonia in foals but does not induce disease in adult horses. Virulence of R. equi depends on the presence of a large plasmid, which encodes a family of seven virulence-associated proteins (VapA and VapC to VapH). Eradication of R. equi from the lungs depends on gamma interferon (IFN-γ) production by T lymphocytes. The objectives of the present study were to determine the relative in vivo expression of the vap genes of R. equi in the lungs of infected foals, to determine the recall response of bronchial lymph node (BLN) lymphocytes from foals and adult horses to each of the Vap proteins, and to compare the cytokine profiles of proliferating lymphocytes between foals and adult horses. vapA, vapD, and vapG were preferentially expressed in the lungs of infected foals, and expression of these genes in the lungs was significantly (P < 0.05) higher than that achieved during in vitro growth. VapA and VapC induced the strongest lymphoproliferative responses for foals and adult horses. There was no significant difference in recall lymphoproliferative responses or IFN-γ mRNA expression by bronchial lymph node lymphocytes between foals and adults. In contrast, interleukin 4 (IL-4) expression was significantly higher for adults than for foals for each of the Vap proteins. The ratio of IFN-γ to IL-4 was significantly higher for foals than for adult horses for most Vap proteins. Therefore, foals are immunocompetent and are capable of mounting lymphoproliferative responses of the same magnitude and cytokine phenotype as those of adult horses.

scholarly journals Reciprocal Protective Immunity againstBordetella pertussis and Bordetella parapertussis in a Murine Model of Respiratory Infection

2001 ◽  
Vol 69 (11) ◽  
pp. 6981-6986 ◽  
Author(s):  
Mineo Watanabe ◽  
Masaaki Nagai
Keyword(s):  
Immune Response ◽  
Respiratory Infection ◽  
Murine Model ◽  
Protective Immunity ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Spleen Cells ◽  
Bordetella Parapertussis ◽  
Ifn Γ

ABSTRACT The protective immunity induced by infection with Bordetella pertussis and with Bordetella parapertussis was examined in a murine model of respiratory infection. Convalescent mice that had been infected by aerosol with B. pertussis or with B. parapertussis exhibited a protective immune response against B. pertussis and also against B. parapertussis. Anti-filamentous hemagglutinin (anti-FHA) serum immunoglobulin G (IgG) and anti-FHA lung IgA antibodies were detected in both mice infected with B. pertussis and those infected with B. parapertussis. Antibodies against pertussis toxin (anti-PT) and against killed B. pertussis cells were detected in mice infected with B. pertussis. Pertactin-specific antibodies and antibodies against killed B. parapertussis cells were detected in mice infected with B. parapertussis. Spleen cells from mice infected with B. pertussis secreted interferon-γ (IFN-γ) in response to stimulation by FHA or PT. Spleen cells from mice infected with B. parapertussis also secreted IFN-γ in response to FHA. Interleukin-4 was not produced in response to any of the antigens tested. The profiles of cytokine secretion in vitro revealed induction of a Th1-biased immune response during convalescence from infection by B. pertussis and byB. parapertussis. It is possible that Th1 and Th2 responses against FHA might be related to the reciprocal protection achieved in our murine model.

scholarly journals Migration-Inhibitory Factor Gene-Deficient Mice Are Susceptible to Cutaneous Leishmania major Infection

2001 ◽  
Vol 69 (2) ◽  
pp. 906-911 ◽  
Author(s):  
Abhay R. Satoskar ◽  
Marcelo Bozza ◽  
Miriam Rodriguez Sosa ◽  
Guoshing Lin ◽  
John R. David
Keyword(s):  
Migration Inhibitory Factor ◽  
Protective Immunity ◽  
Leishmania Major ◽  
Inhibitory Factor ◽  
Interleukin 4 ◽  
Wild Type ◽  
Leishmanicidal Activity ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT To determine the role of endogenous migration-inhibitory factor (MIF) in the development of protective immunity against cutaneous leishmaniasis, we analyzed the course of cutaneous Leishmania major infection in MIF gene-deficient mice (MIF−/−) and wild-type (MIF+/+) mice. Following cutaneous L. major infection, MIF−/− mice were susceptible to disease and developed significantly larger lesions and greater parasite burdens than MIF+/+ mice. Interestingly, antigen-stimulated lymph node cells from MIF−/− mice produced more interleukin-4 (IL-4) and gamma interferon (IFN-γ) than those from MIF+/+ mice, although the differences were statistically not significant. IFN-γ-activated resting peritoneal macrophages from MIF−/− mice showed impaired macrophage leishmanicidal activity and produced significantly lower levels of nitric oxide and superoxide in vitro. The macrophages from MIF−/− mice, however, produced much more IL-6 than macrophages from wild-type mice. These findings demonstrate that endogenous MIF plays an important role in the development of protective immunity against L. majorin vivo. Furthermore, they indicate that the susceptibility of MIF−/− mice to L. major infection is due to impaired macrophage leishmanicidal activity rather than dysregulation of Th1 and Th2 responses.

Drug cost and outcome in metastatic colorectal cancer with emphasis on monoclonal antibodies.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 567-567
Author(s):  
Helmy M. Guirgis
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Drug Cost ◽  
Outcome Evaluation ◽  
Wild Type ◽  
First Line ◽  
Significant Difference ◽  
Number Of Cycles ◽  
The Cost

567 Background: Patients with wild type KRAS metastatic colorectal cancer (mCRC), treated with first-line cetuximab (Cet) or bevacizumab (Bev) and chemotherapy demonstrated similar overall survival (OS). In the Western world, costs of anticancer drugs ranged from $59,000 to $100,000 per life-year gain (LYG). Hazard ratios (HR) have rarely been integrated in cost/outcome evaluation. Objective: Weigh drug cost against survival and hazard ratio (HR) in mCRC with emphasis on monoclonal antibodies (MABs). Methods: Estimated costs in United States dollars (US$) were calculated for 70 kg or 1.7/m2 patients. Costs were divided by the reported median OS gain over control in days (OSg) and by probability of survival (PoS) calculated as (1.0 – HR). Relative values (RV) were computed as 100,000/cost/outcome. Results: There was no significant difference in cost/outcome of Pan and Cet in first-line wild KRAS mCRC. At 12 week (w), the cost/LYG of panitumumab (Pan), Cet, and Bev were $64,947, $82,224, and $36,919 with RVs of 1.54, 1.22 and 2.71 respectively. Using HRs, the corresponding PoS were $140,082, $137,040, and $42,524 with RVs of 0.71, 0.73, and 2.35. Wild RAS testing improved the cost/outcome of Pan by 25%. Increasing number of cycles increased the cost/outcome and decreased the RVs of all MOAs. Conclusions: In first-line wild KRAS mCRC at 12 w, the cost/outcome of Bev was approximately 30% to 57% that of Pan and Cet. Cost/outcome of Pan significantly improved in RAS wild type. The cost/outcome of MABs was determined by the number of cycles.

scholarly journals Anisakis pegreffii-Induced Airway Hyperresponsiveness Is Mediated by Gamma Interferon in the Absence of Interleukin-4 Receptor Alpha Responsiveness

2010 ◽  
Vol 78 (9) ◽  
pp. 4077-4086 ◽  
Author(s):  
Frank Kirstein ◽  
William G. C. Horsnell ◽  
Natalie Nieuwenhuizen ◽  
Bernhard Ryffel ◽  
Andreas L. Lopata ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Airway Hyperresponsiveness ◽  
Allergic Airway Inflammation ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Wild Type ◽  
Receptor Alpha ◽  
Immunological Mechanisms ◽  
Ifn Γ ◽  
Interleukin 4 Receptor

ABSTRACT Infection with the fish parasite Anisakis following exposure to contaminated fish can lead to allergic reactions in humans. The present study examined the immunological mechanisms underlying the development of allergic airway inflammation in mice after different routes of sensitization to Anisakis. Wild-type and interleukin-4 receptor alpha (IL-4Rα)-deficient BALB/c mice were sensitized intraperitoneally with live or heat-killed Anisakis larvae or by intranasal administration of an Anisakis extract and were subsequently challenged intranasally with an Anisakis extract. Both routes of sensitization induced IL-4Rα-dependent allergic airway responses, whereas allergen-specific antibody responses developed only when mice were sensitized intraperitoneally. Intranasal sensitization induced airway hyperresponsiveness (AHR) in wild-type mice only, showing that AHR was IL-4/IL-13 dependent. Unexpectedly, infection with Anisakis larvae induced AHR in both wild-type and IL-4Rα-deficient mice. IL-4Rα-independent AHR was mediated by gamma interferon (IFN-γ), as evidenced by the fact that in vivo neutralization of IFN-γ abrogated AHR. Together, these results demonstrate that both infection with larvae and inhalational exposure to Anisakis proteins are potent routes of allergic sensitization to Anisakis, explaining food- and work-related allergies in humans. Importantly for diagnosis, allergic airway inflammation can be independent of detectable Anisakis-specific antibodies. Moreover, depending on the route of sensitization, AHR can be induced either by IL-4/IL-13 or by IFN-γ.

Cilostazol Mediates Immune Responses and Affects Angiogenesis During the Acute Phase of Hind Limb Ischemia in a Mouse Model

2020 ◽  
Vol 25 (3) ◽  
pp. 273-285 ◽  
Author(s):  
Efthymios Paronis ◽  
Michalis Katsimpoulas ◽  
Nikolaos P. E. Kadoglou ◽  
Claire Provost ◽  
Marianna Stasinopoulou ◽  
...  
Keyword(s):  
Immune Cells ◽  
Hind Limb ◽  
Limb Ischemia ◽  
Histological Evaluation ◽  
Wild Type ◽  
Hind Limb Ischemia ◽  
Tnf Α ◽  
Significant Difference ◽  
Significant Augmentation ◽  
Ifn Γ

Background: Cilostazol is a drug of choice for the treatment of intermittent claudication that also affects innate and adaptive immune cells. The purpose of our study was the evaluation of cilostazol’s impact on the immune and angiogenic response in murine models of hind limb ischemia. Methods: We used 108 immunodeficient NOD.CB17-Prkdcscid/J mice and 108 wild-type CB17 mice. At day 0 (D0), all animals underwent hind limb ischemia. Half of them in both groups received daily cilostazol starting at D0 and for the next 7 postoperative days, while the rest of them served as controls, receiving vehicle. Interleukin (IL) 2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) serum concentrations were measured by flow cytometry on postsurgery days D1, D3, D5, and D7. On D7, both groups underwent positron emission tomography scan with 68Ga-RGD. Mice were euthanatized and gastrocnemius muscles were obtained for histological evaluation. Results: There was a statistically significant augmentation ( P < .05) in IL-4, IL-10, IL-6, and IFN-γ concentrations in treated CB17 animals, while IL-2 was significantly suppressed. Significant difference was detected between the CiBisch and Bisch groups on D1 and D7 ( P < .05) in CD31 staining. In treated NOD.CB17 animals, TNF-α, IL-6, and IFN-γ presented significant augmentation, while 68Ga-NODAGA-RGDfK uptake and CD31 expression were found significantly lower for both legs in comparison to the control. Conclusion: Cilostazol seems to significantly increase angiogenesis in wild-type animals during the first postoperational week. It also influences immune cells, altering the type of immune response by promoting anti-inflammatory cytokine production in wild-type animals, while it helps toward inflammation regression in immunodeficient animals.

scholarly journals Critical Role of Cytotoxic T Lymphocytes in Immune Clearance of Rickettsial Infection

2001 ◽  
Vol 69 (3) ◽  
pp. 1841-1846 ◽  
Author(s):  
David H. Walker ◽  
Juan P. Olano ◽  
Hui-Min Feng
Keyword(s):  
T Lymphocytes ◽  
Knockout Mice ◽  
Gene Knockout ◽  
Wild Type ◽  
Spleen Cells ◽  
Rickettsial Infection ◽  
Cd8 T Lymphocytes ◽  
Gene Knockout Mice ◽  
Ifn Γ ◽  
Ctl Activity

ABSTRACT Cytotoxic T-lymphocyte (CTL) activity developed against the major infected target cells of rickettsial infections, endothelial cells and macrophages. Spleen cells from mice immune to Rickettsia conorii exerted specific major histocompatibility complex (MHC) class I-matched CTL activity against R. conorii-infected SVEC-10 endothelial cells, with peak activity on day 10. Similarly, spleen cells from Rickettsia australis-immune mice exerted specific CTL activity against an R. australis-infected macrophage-like cell line. Gamma interferon (IFN-γ) gene knockout mice were more than 100-fold more susceptible to R. australis infection than wild-type C57BL/6 mice. MHC class I gene knockout mice were the most susceptible, more than 50,000-fold more susceptible to a lethal outcome of R. australis infection than wild-type C57BL/6 mice. These results indicate that CTL activity was more critical to recovery from rickettsial infection than were the effects of IFN-γ. The observation that perforin gene knockout mice were more than 100-fold more susceptible than wild-type C57BL/6 mice indicates that perforin-mediated activity accounts for a large component, but not all, of the CTL-mediated antirickettsial effect. CTL activity was expressed by immune CD8 T lymphocytes. Adoptive transfer of immune CD8 T lymphocytes from IFN-γ gene knockout mice intoR. australis-infected IFN-γ gene knockout mice dramatically reduced the infectious rickettsial content in the organs, confirming that CD8 T lymphocytes provide immunity against rickettsiae besides that provided by the secretion of IFN-γ. CTLs appear to be crucial to recovery from rickettsial infection.

Interferon-γ: a key contributor to hyperoxia-induced lung injury in mice

2004 ◽  
Vol 287 (5) ◽  
pp. L1042-L1047 ◽  
Author(s):  
Mitsuhiro Yamada ◽  
Hiroshi Kubo ◽  
Seiichi Kobayashi ◽  
Kota Ishizawa ◽  
Hidetada Sasaki
Keyword(s):  
Lung Injury ◽  
Cell Activation ◽  
Late Phase ◽  
Neutrophil Migration ◽  
Lavage Fluid ◽  
Interferon Γ ◽  
Wild Type ◽  
Permeability Changes ◽  
Significant Difference ◽  
Ifn Γ

Hyperoxia-induced lung injury complicates the care of many critically ill patients who receive supplemental oxygen therapy. Hyperoxic injury to lung tissues is mediated by reactive oxygen species, inflammatory cell activation, and release of cytotoxic cytokines. IFN-γ is known to be induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. To determine whether IFN-γ contributes to hyperoxia-induced lung injury, we first used anti-mouse IFN-γ antibody to blockade IFN-γ activity. Administration of anti-mouse IFN-γ antibody inhibited hyperoxia-induced increases in pulmonary alveolar permeability and neutrophil migration into lung air spaces. To confirm that IFN-γ contributes to hyperoxic lung injury, we then simultaneously exposed IFN-γ-deficient (IFN-γ−/−) mice and wild-type mice to hyperoxia. In the early phase of hyperoxia, permeability changes and neutrophil migration were significantly reduced in IFN-γ−/− mice compared with wild-type mice, although the differences in permeability changes and neutrophil migration between IFN-γ−/− mice and wild-type mice were not significant in the late phase of hyperoxia. The concentrations of IL-12 and IL-18, two cytokines that play a role in IFN-γ induction, significantly increased in bronchoalveolar lavage fluid after exposure to hyperoxia in both IFN-γ−/− mice and wild-type mice, suggesting that hyperoxia initiates upstream events that result in IFN-γ production. Although there was no significant difference in overall survival, IFN-γ−/− mice had a better early survival rate than did the wild-type mice. Therefore, these data strongly suggest that IFN-γ is a key molecular contributor to hyperoxia-induced lung injury.

scholarly journals Predominance of CD4 Th1 and CD8 Tc1 Cells Revealed by Characterization of the Cellular Immune Response Generated by Immunization with a DNA Vaccine Containing a Trypanosoma cruzi Gene

1999 ◽  
Vol 67 (8) ◽  
pp. 3855-3863 ◽  
Author(s):  
Mauricio M. Rodrigues ◽  
Marcelo Ribeirão ◽  
Vera Pereira-Chioccola ◽  
Laurent Renia ◽  
Fabio Costa
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Dna Vaccine ◽  
Cd8 T Cells ◽  
Catalytic Domain ◽  
Therapeutic Vaccine ◽  
Cell Types ◽  
Interleukin 4 ◽  
Ifn Γ

ABSTRACT Immunization with a plasmid DNA containing the gene encoding the catalytic domain of trans-sialidase (TS) elicits protective immune responses against experimental Trypanosoma cruziinfection. As several studies provided strong evidence that during infection CD4 Th1 and CD8 T cytotoxic type 1 (Tc1) cells are important factors in host resistance, the present study was designed to evaluate which T-cell types were activated in DNA-vaccinated BALB/c mice. We found that bulk cells from DNA-immunized mice had CD4 and CD8 T cells that produced gamma interferon (IFN-γ) but not interleukin-4 (IL-4) or IL-10. To characterize the TS-specific T cells at the clonal level, we generated CD4 and CD8 clones. We obtained cytotoxic CD4 clones of the Th1 type that secreted large amounts of IFN-γ but not IL-4 or IL-10. Unexpectedly, we obtained other CD4 clones with a Th2 phenotype, secreting IL-4 and IL-10 but not IFN-γ. All CD8 clones were cytotoxic and produced IFN-γ. IL-4 and IL-10 were not secreted by these cells. Using synthetic peptides, we determined a CD8 epitope recognized by several clones as being represented by amino acids IYNVGQVSI. The antiparasitic activity of a CD4 Th1 and a CD8 Tc1 clone was assessed in vitro. CD4 or CD8 T cells significantly inhibited T. cruzidevelopment in infected macrophages or fibroblasts, respectively. We concluded that DNA vaccine efficiently generates potentially protective CD4 Th1 and CD8 Tc1 cells specific for a T. cruzi antigen, therefore reinforcing the possibility of using this strategy for developing a preventive or therapeutic vaccine against Chagas’ disease.

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