Enhanced IL-10 Production<i>In Vitro</i>by Monocytes in Autoimmune Haemolytic Anaemia

Fagiolo, E; Terenzi, Caterina Toriani

doi:10.3109/08820139909062268

Cited by 9 publications

(5 citation statements)

References 13 publications

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“…These results differ from those reported in another study of IMHA in dogs [39] and from in vitro studies of PBMCs from people with wIMHA [28,47,48], in which the concentration of IL-10 was increased in affected individuals. Interleukin 10 is considered to be an important regulatory cytokine, yet serum concentrations appear to be paradoxically high in diseases characterised by production of autoantibodies, including AIHA and systemic lupus erythematosus (SLE) [49].…”

Section: Discussioncontrasting

confidence: 99%

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Swann

Woods

et al. 2016

PLoS ONE

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BackgroundImmune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.AimsTo investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.Animals19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.MethodsResidual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.ResultsThere was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.ConclusionsThe immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA.

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Section: Discussioncontrasting

confidence: 99%

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Swann

Woods

et al. 2016

PLoS ONE

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“…A similar phenomenon has been observed in the course of hemolytic anemia in autoimmune diseases in which monocytes stimulated with LPS showed a decreased production of IL-10 compared to controls. 43 It is noteworthy, that SLE-associated disturbances of phagocytosis might be even more pronounced in untreated SLE, as all of the patients in this study were treated with some form of immunosuppressive treatment. However, these treatments clearly are insufficient to normalize apoptotic cell phagocytosis and do not prevent development of organ changes.…”

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Characterization of the impairment of the uptake of apoptotic polymorphonuclear cells by monocyte subpopulations in systemic lupus erythematosus

Mikołajczyk

Skiba

Batko

et al. 2014

Lupus

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Efficient removal of apoptotic polymorphonuclear leukocytes (PMNs) is an important step in the resolution of inflammation, which protects tissues from the noxious contents of dying cells. While the impairment of apoptotic PMNs removal has been demonstrated for macrophages in systemic lupus erythematosus (SLE), recent studies show that monocytes are also capable of such phagocytosis, although their involvement in SLE is not clear. Therefore, we characterized phagocytosis of apoptotic PMNs by monocytes in 22 patients with SLE and 22 healthy controls. Using flow cytometry we demonstrate that in SLE peripheral blood monocytes show impaired phagocytosis of autologous apoptotic PMNs, while they efficiently engulf apoptotic PMNs isolated from healthy subjects. Monocytes CD14highCD16+ and CD14dimCD16+ more efficiently interacted with apoptotic neutrophils than CD16- cells both in SLE and healthy subjects. Monocytes in SLE showed modestly decreased expression of CD35 and CD91 and increased expression of T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3); however, these differences were evident mainly in selected subsets of monocytes (CD16+) while defects in phagocytosis were observed in all monocyte subsets. Apoptotic cell-dependent induction of lipopolysaccharide (LPS) stimulated production of anti-inflammatory cytokine IL-10 by peripheral blood mononuclear cells (PBMC) was blunted in SLE while the production of pro-inflammatory cytokine TNF-α was unchanged.

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“…Some studies evaluate PBMC cultures' proliferative response and IL‐10, IL‐12, IL‐IL‐2, IL‐4, and IFN‐γ production, respectively, by 3 H‐thymidine incorporation and ELISA under basal conditions and after mitogen stimulation (LPS, PHA, and OKT3) 34,42,43. In untreated AIHA, patients have shown, in basal conditions, a proliferative response greater than that of controls, suggesting a basal state of hyperactivation.…”

Section: Disorders Of Immunoregulationmentioning

confidence: 99%

“…Furthermore, several cytokines (for instance, IL‐4, IL‐6, and IL‐10) are known to promote Ab production. It has been suggested that Th2 cells might play a role in the development of various autoAb‐mediated diseases such as systemic lupus erythematosus (SLE) and AIHA 32‐34. IL‐12, mostly produced by activated monocytes, promotes the development of Th1 cells in vitro and in vivo and may inhibit IL‐4‐induced Ab production 35.…”

Section: Disorders Of Immunoregulationmentioning

confidence: 99%

IL-10 and the Cytokine Network in the Pathogenesis of Human Autoimmune Hemolytic Anemia

Toriani-Terenzi

Fagiolo

2005

Annals of the New York Academy of Sciences

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In animal and human autoimmune hemolytic anemia (AIHA) immunologic tolerance loss against RBC self-antigens could be originated by several mechanisms: ignored self-antigens' epitopes, polyclonal lymphocyte activation, molecular mimicry between self- and foreign antigens, central or peripheral tolerance errors, or immunoregulatory disturbances including the alteration of a cytokine network. To identify the immunologic factors contributing to autoimmune onset and maintenance, several murine strains (such as NZB and NZB/NZW) that spontaneously develop a complex autoimmune syndrome, including AIHA, have been extensively studied. In human AIHA, the respective roles of IL-2, IL-4, IFN-gamma, IL-10, and IL-12 were investigated by examining the spontaneous and mitogen-induced (OKT3 or LPS) production of these cytokines. ELISA methods were used in PBMCs to evaluate whether the manipulation of IL-10/IL-12 balance can have an effect on the incidence of autoimmune diseases and whether this might be useful for the control of AIHA. Results affirmed that AIHA is a disease that exhibits an increased basal synthesis of IL-4 and decreased levels of IFN-gamma by AIHA PBMCs compared with controls and that there is a basal increase of Th2 cytokines. Th1-type cytokine decrease in the basal state occurred in parallel with an increase of constitutive IL-10 production and an IL-12 decrease. In conclusion, decreased production of Th1-type cytokines and the production of autoantibodies in AIHA may be secondary to the imbalance between IL-10 and IL-12, and the neutralization of IL-10 may be efficacious in diminishing the clinical pathology associated with Th2 subset prevalence. In the same way, the treatment with IL-12 could offer a second and independent level of blockade against the consequences of the overstimulation of B cells associated with AIHA.

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Enhanced IL-10 ProductionIn Vitroby Monocytes in Autoimmune Haemolytic Anaemia

Cited by 9 publications

References 13 publications

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Characterization of the impairment of the uptake of apoptotic polymorphonuclear cells by monocyte subpopulations in systemic lupus erythematosus

IL-10 and the Cytokine Network in the Pathogenesis of Human Autoimmune Hemolytic Anemia

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