Expression of interferon-gamma and tumor necrosis factor-alpha in bone marrow T cells and their levels in bone marrow plasma in patients with aplastic anemia.
Immune-mediated stem cell damage has been postulated to be responsible for disease initiation and progression in aplastic anemia (AA). It is hypothesized that T lymphocytes play a major role in destroying the bone marrow (BM) stem cells of AA patients by infiltrating the BM and secreting excessive levels of anti-hematopoietic cytokines, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). We undertook this study to assess the pathogenic significance of anti-hematopoietic cytokines such as IFN-gamma and TNF-alpha in BM T cells and plasma of AA patients. Significantly elevated levels of IFN-gamma and TNF-alpha were found in the BM plasma of AA patients compared to controls (p=0.05 and 0.006, respectively). Intracellular IFN-gamma and not TNF-alpha in BM CD3+ T cells of AA patients was significantly higher compared to controls (p=0.04 and p=0.2, respectively). A follow-up analysis of expression of these cytokines in BM T cells and their levels in BM plasma in five AA patients before and 180 days (6 months) after antithymocyte globulin (ATG) and cyclosporin A (CsA) therapy showed a decline 180 days after therapy compared to pre-therapy. We thus conclude that increased production of both IFN-gamma and TNF-alpha in the BM may contribute to disease pathogenesis in AA and ATG therapy may induce hematological remission by suppressing the elevated levels of IFN-gamma and TNF-alpha in AA BM.
Dubey
Shweta
S
Department of Immunology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences (SGPGIMS), Raebareli Road, Lucknow, 226014, India.
Shukla
Priyanka
P
Nityanand
Soniya
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000209:etiology / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000494:pharmacology / Q000627:therapeutic use; D001853:Bone Marrow / Q000098:blood supply / Q000276:immunology*; D017252:CD3 Complex; D016022:Case-Control Studies; D002648:Child; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000961:Antilymphocyte Serum; D017252:CD3 Complex; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016572:Cyclosporine