interleukin-8 and Anemia--Aplastic

The immune-induced aplastic anemia (AA) mouse model has been used for the study of AA. However, there were no uniform conditions for establishing a model and no assessment of immunological homeostasis. Our study aimed to identify the conditions of establishing a model and assess the AA model in immunology and pathology.. We induced an AA mouse model by the combination between sublethal irradiation and spleen-thymus lymphocyte infusion. The success of establishing the AA model was identified by blood routine tests and pathology of bone marrow. The frequency of Th17 and Treg cells was measured by flow cytometry. The frequency of CD34+ and CD41+ cells was detected by immunohistochemical technique.IL-6, IL-8, IL-17, TNF-α and IFN-γ were evaluated by ELISA.. The. Our data suggest that the improved AA mouse model conforms to the diagnosis standard of AA and simulates the immune internal environment of human AA. The AA mouse model has a longer lifetime and unbalances of Th17/Treg cells caused the destruction of CD34+ cells and CD41+ cells, which was immune-mediated pathogenesis to adapt to long-term research.

Topics: Anemia, Aplastic; Animals; Disease Models, Animal; Humans; Interleukin-17; Interleukin-6; Interleukin-8; Mice; Pancytopenia; Spleen; Th17 Cells; Tumor Necrosis Factor-alpha

Although aplastic anemia (AA) does not come under the category of blood malignant diseases, the infection that frequently occurs in this bone marrow failure can make it worse. Pulmonary infection is the most prevalent but limiting clinical diagnosis. To find biomarkers predicting bacterial or bacterial-combined fungal infections in the lungs, we reviewed 287 AA medical records including 151 without any infection, 87 with pure pulmonary bacterial infection, and 49 with bacterial and fungal infection were reviewed. There were substantial changes in IL-17F, IL-17A, IFN-γ, IL-6, IL-8, and IL-10 levels between the non-infected and lung bacterial infection groups (P < 0.05). Further, a significant variation in IL-17A, TNF-β, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-22, and IL-12p70, between the uninfected group and the pulmonary bacterial and fungal infection group (P < 0.05) was observed. The results further revealed significant differences in TNF-β, IL-12p70, IL-6, IL-8, and IL-10 between the pulmonary bacterial infection group and the fungal infection group (P < 0.05). Moreover, by calculating ROC and cut-off values, we determined that IL-6 (AUC = 0.98, Cut-off = 14.28 pg/ml, P = 0.0000) had a significant advantage than other cytokines, body temperature (AUC = 0.61, P = 0.0050), PCT (AUC = 0.57, P = 0.0592), and CRP (AUC = 0.60, P = 0.0147) in the detection of lungs bacterial infections. In addition, IL-6 (AUC = 1.00, Cut-off = 51.50 pg/ml, P = 0.000) and IL-8 (AUC = 0.87, Cut-off = 60.53 pg/ml, P = 0.0000) showed stronger advantages than other cytokines, body temperature (AUC = 0.60, P = 0.0324), PCT (AUC = 0.72, Cut-off = 0.63 ng/ml, P = 0.0000) and CRP (AUC = 0.79, Cut-off = 5.79 mg/l, P = 0.0000) in distinguishing bacteria from fungi. This may suggest that IL-8 may play a role in differentiating co-infected bacteria and fungi. Such advantages are repeated in severe aplastic anemia (SAA) and very severe aplastic anemia (VSAA).In conclusion, aberrant IL-6 elevations in AA patients may predict the likelihood of bacterial lung infection. The concurrent increase of IL-6 and IL-8, on the other hand, should signal bacterial and fungal infections in patients.These findings may help to suggest bacterial or fungal co-infection in patients with AA (Focus on VSAA and SAA).

Topics: Anemia, Aplastic; Bacteria; Bacterial Infections; Coinfection; Cytokines; Humans; Interleukin-10; Interleukin-12; Interleukin-17; Interleukin-6; Interleukin-8; Lung; Lymphotoxin-alpha; Mycoses

The aim of this study was to evaluate the levels of interleukin (IL)-6 and IL-8 in patients with aplastic anemia and its correlation with severity of the disease.. IL-6 and IL-8 levels were measured in 40 patients with aplastic anemia in the age group of 4 to 14 years. A total of 40 healthy children served as controls. Quantitative estimation of IL-6 and IL-8 was performed using a solid-phase sandwich ELISA kit. Results were presented as IL-6 and IL-8 concentrations in pg/mL. Patients received immunosuppressive therapy per the British Committee for Standards in Haematology Guidelines 2009.. Mean age of the patients was 9.78±2.74 years. IL-6 level of patients was elevated compared with controls (193.48±352.3 vs. 4.58±3.39; P<0.001). IL-8 levels were also significantly elevated in patients compared with controls (15.58±18.0 vs. 1.85±0.95; P<0.001). IL levels were also assessed in relation to severity of the disease. Levels were the highest in patients with very severe aplastic anemia (724.33±519.42), followed by severe aplastic anemia (80.51±66.28 pg/mL), and non-severe aplastic anemia (6.01±1.89). Differences were statistically significant. A similar trend was also observed for IL-8 levels, where the levels were 41.02±24.23, 11.34±8.0, and 1.67±0.71 for very severe aplastic anemia, severe aplastic anemia, and non-severe aplastic anemia, respectively. The differences were again statistically significant. IL levels were also correlated with the treatment outcome. Responders had lower levels compared with nonresponders, but the difference was not statistically significant (186.36±322.45 vs. 198.74±368.10). Levels of ILs decreased in responders, but were not comparable with that of controls 6 months after therapy.. High levels of IL-6 and IL-8 were observed in children with aplastic anemia. Increased levels showed correlation with disease severity and therefore appear to play an important role in aplastic anemia. However, levels had no significant correlation with the treatment outcome.

Topics: Adolescent; Anemia, Aplastic; Case-Control Studies; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Humans; Immunosuppressive Agents; Interleukin-6; Interleukin-8; Severity of Illness Index

Cytokines IL-2 and IL-8 both participate in immune regulation. However, the relationship between polymorphisms in these two cytokines and the risk of acquired aplastic anemia (acquired AA) has not been explored.. We selected five SNPs including rs11575812, rs2069772 and rs2069762 of IL-2, rs2227306 and rs2227543 of IL-8. SNaPshot genotyping was used to test the genotypes of IL-2 and IL-8 polymorphisms in a population of 101 acquired AA patients and 165 healthy controls.. The rs2069762 G allele appeared to be a protective mutation, but no significant differences were found in other four SNPs. We also found that rs2069762 had an impact on the transcriptional regulation.. It could be assumed that the rs2069762 polymorphism might reduce the risk of acquired aplastic anemia, while the remaining four SNPs might not contribute to susceptibility to acquired AA in a Chinese population.

Topics: Adolescent; Adult; Alleles; Anemia, Aplastic; Asian People; Case-Control Studies; Child; Child, Preschool; Gene Expression; Gene Frequency; Genotype; Humans; Interleukin-2; Interleukin-8; Middle Aged; Polymorphism, Single Nucleotide; Risk

Aplastic anaemia (AA) is thought to be an autoimmune-mediated disease with active destruction of haematopoietic cells through a T helper type 1 (Th1) cell response. Interleukin (IL)-17 is a potent proinflammatory cytokine produced by activated memory T cells. Recent studies indicate that IL-17 might be an essential effector cytokine in the T-cell mediated autoimmune process. It can drive the production of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6 and IL-8 by a variety of cells. The present study investigated the genetic and protein expression of IL-17 in patients with AA. The effect of IL-17 on IL-6 and IL-8 production by macrophages was also studied. AA patients showed an elevated expression of IL17A mRNA in bone marrow mononuclear cells and peripheral blood mononuclear cells. Higher IL-17 in bone marrow and peripheral blood plasma was also observed in AA patients compared with normal controls. IL-17 induced the production of IL-6 and IL-8 by macrophages both from patients with AA and normal controls. IL-17 stimulation also resulted in the production of TNF-alpha. These results suggested that elevated expression of IL-17 and IL-17-induced IL-6, IL-8 and TNF-alpha may be involved in the mechanisms of AA.

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Case-Control Studies; Cells, Cultured; Female; Humans; Interleukin-17; Interleukin-6; Interleukin-8; Macrophages; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Up-Regulation; Young Adult

Interleukin-8 (IL-8), a CXC chemokine, is also a potent inhibitor of myelopoiesis, the hematopoietic process that is severely impaired in aplastic anemia (AA). To elucidate its role in the disease, we have investigated levels of IL-8 by quantitative enzyme-linked immunosorbent assay in bone marrow and peripheral blood plasma of 27 AA patients and in the marrow of 16 controls and blood of 20 controls. Significantly increased levels of IL-8 were observed in the marrow and blood of patients as compared to controls (470.4 +/- 549.6 vs. 37.5 +/- 30.3; P < 0.0001) and (247.3 +/- 286.3 vs. 7.9 +/- 5.5; P < 0.0001), respectively. Among the patients, the IL-8 levels were higher in patients with severe AA than those with nonsevere AA in the marrow (568.8 +/- 586.9 vs. 126.3 +/- 102.5; P < 0.005) as well as in the blood (296.6 +/- 305.5 vs. 75.0 +/- 84.4; P < 0.008) plasma. The marrow and blood of 74% (20/27) of the patients had increased levels of IL-8 compared to 12% (2/16; P < 0.001) and 10% (2/20, P < 0.001) of the controls, respectively. These results suggest that IL-8 may have an important role in the pathogenesis of AA.

Topics: Adolescent; Adult; Anemia, Aplastic; Bone Marrow; Case-Control Studies; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged; Severity of Illness Index; Up-Regulation

To evaluate the effects of cellular immune function and cytokines on the pathogenesis of aplastic anemia (AA) and its clinical significance.. T lymphocyte subsets and HLA-DR antigen expression in the peripheral blood cells were assayed, and the levels of G-CSF, IL-6, TNF alpha, IFN alpha and IL-8 in the PBMNC culture supernatants were determined in 38 AA patients and 20 normal control with APAAP and ELISA methods.. CD4+ cells, CD4+/CD8+ cells and G-CSF level were lower, and CD8+ cells, HLA-DR+ cells and IL-6, TNF alpha, IFN alpha and IL-8 levels were higher in AA patients than in normal controls. The level of G-CSF was positively correlated with CD4+ cells and CD4+/CD8+ cells and negatively with IFN alpha level. IL-6 level was negatively correlated with WBC count and CD4+ cells. TNF alpha level was positively correlated with CD8+ cells and negatively with CD4+/CD8+ cells. IL-8 level was positively correlated with CD8+ cells and HLA-DR+ cells.. The cellular immune dysfunction and cytokine aberration participate in the pathogenesis of AA.

Topics: Adult; Anemia, Aplastic; Enzyme-Linked Immunosorbent Assay; Female; Granulocyte Colony-Stimulating Factor; HLA-DR Antigens; Humans; Immunity, Cellular; Interleukin-8; Male; T-Lymphocyte Subsets

To investigate the role of interleukin-8 in the pathogenesis of aplastic anemia (AA) and its correlation with clinical status.. Serum level of IL-8 in 24 AA patients and 20 normal controls was measured by sandwich enzyme linked immunosorbent assay(ELISA).. The levels of IL-8 were increased significantly(P < 0.05) in AA patients than in normal controls, and the IL-8 levels in severe AA group were much higher than those in chronic AA group (P < 0.05). Serum IL-8 in AA patients with infection were elevated significantly(P < 0.005).. IL-8 may have a potential role in the pathogenesis of AA and determination of serum IL-8 may be helpful for evaluation of severity and infectious complication of AA.

Topics: Adolescent; Adult; Anemia, Aplastic; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged

We studied mRNA expression of the cytokine granulocyte-colony stimulating factor (G-CSF), interleukin-1 beta (IL-1 beta), IL-6, IL-8 and stem cell factor of stromal cells derived from bone marrows of nine normal volunteers, eight patients with aplastic anaemia (AA) and seven patients with myelodysplastic syndrome (MDS). The proportion of endothelial cells, macrophages, fibroblast-like cells and adipocytes in stromal cells showed no differences between normal volunteers and the patients. Levels of cytokine mRNA expression were determined by reverse transcription-polymerase chain reaction. Spontaneous expression occurred and this was augmented by LPS stimulation in cells of all the normal volunteers and in most patients. When stimulated by LPS, the mean G-CSF and IL-1 beta mRNA expressions in patients with AA were significantly higher than normal volunteers, but there was one patient showing lower IL-1 beta, IL-6 and IL-8 expression with no response to LPS. LPS-induced IL-6 and IL-8 expression of two patients with MDS were significantly higher than normal. The spontaneous and LPS-induced protein concentration of G-CSF, IL-6 and IL-8 in culture supernatants from 15, 10 and four patients, correlated well with the mRNA expression. The correlation coefficients were 0 x 92, 0 x 78 and 0 x 91, respectively. In conclusion, there were a few patients whose aetiology appeared to be reduction of stromal cytokine expression in AA, but most patients with AA and MDS expressed normal or high levels of cytokine mRNA.

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Myelodysplastic Syndromes; Polymerase Chain Reaction; RNA, Messenger; Stem Cells; Stromal Cells