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Production of hematopoietic regulatory cytokines by peripheral blood mononuclear cells in patients with aplastic anemia.
Exp Hematol. 1996 Jan; 24(1):31-6.EH

Abstract

The aim of this study was to measure the level of cytokines produced by peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA) and determine their effect on normal bone marrow (BM) colony growth. Thirty-five patients with AA and 21 normal controls were enrolled in the study. Medium conditioned by PBMNC of AA patients in the presence of phytohemagglutinin (PHA) was found to be suppressive to the clonal growth of normal BM cells. Thus, we further determined the presence in the PBMNC conditioned medium (CM) of inhibitory cytokines (macrophage inflammatory protein-1 alpha [MIP-1 alpha], transforming growth factor-beta 2 [TGF-beta 2], interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and stimulatory cytokines (granulocyte-macrophage colony-stimulatory factor [GM-CSF], interleukin-3 [IL-3], and stem cell factor [SCF]). The results show no significant difference between AA patients and normal controls in the spontaneous production of all cytokines by PBMNC. After PHA stimulation, the production of MIP-1 alpha, IFN-gamma, TNF-alpha, and GM-CSF significantly increased in the cultures of AA patients (p = 0.0009, 0.0002, 0.0022, and 0.0156, respectively). However, both TGF-beta 2 and SCF were undetectable in most of the tested samples. IL-3 was measured in the conditioned medium only after PHA stimulation, but without significant difference between the two groups (p = 0.67). Furthermore, the myelopoietic suppressing effect of AA-PBMNC CM could be significantly blocked by pretreatment with specific antibodies to the corresponding inhibitory cytokines (MIP-1 alpha, IFN-gamma, and TNF-alpha). After antibody neutralization, an apparent change occurred in the clonal growth of normal BM cells incubated with AA-PBMNC CM, resulting in colony enhancement of 205, 131, and 237% by anti-MIP-1 alpha, anti-IFN-gamma, and anti-TNF-alpha, respectively. These results suggest that overproduction of inhibitory cytokines, rather than underproduction of stimulating cytokines, may play a role in the progression of at least some patients with AA.

Authors+Show Affiliations

Division of Hematology, Veterans General Hospital, Shih-pai, Taipei, Taiwan, Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8536789

Citation

Hsu, H C., et al. "Production of Hematopoietic Regulatory Cytokines By Peripheral Blood Mononuclear Cells in Patients With Aplastic Anemia." Experimental Hematology, vol. 24, no. 1, 1996, pp. 31-6.
Hsu HC, Tsai WH, Chen LY, et al. Production of hematopoietic regulatory cytokines by peripheral blood mononuclear cells in patients with aplastic anemia. Exp Hematol. 1996;24(1):31-6.
Hsu, H. C., Tsai, W. H., Chen, L. Y., Hsu, M. L., Ing-Tiau Kuo, B., Ho, C. H., Lin, C. K., & Wang, S. Y. (1996). Production of hematopoietic regulatory cytokines by peripheral blood mononuclear cells in patients with aplastic anemia. Experimental Hematology, 24(1), 31-6.
Hsu HC, et al. Production of Hematopoietic Regulatory Cytokines By Peripheral Blood Mononuclear Cells in Patients With Aplastic Anemia. Exp Hematol. 1996;24(1):31-6. PubMed PMID: 8536789.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Production of hematopoietic regulatory cytokines by peripheral blood mononuclear cells in patients with aplastic anemia. AU - Hsu,H C, AU - Tsai,W H, AU - Chen,L Y, AU - Hsu,M L, AU - Ing-Tiau Kuo,B, AU - Ho,C H, AU - Lin,C K, AU - Wang,S Y, PY - 1996/1/1/pubmed PY - 1996/1/1/medline PY - 1996/1/1/entrez SP - 31 EP - 6 JF - Experimental hematology JO - Exp Hematol VL - 24 IS - 1 N2 - The aim of this study was to measure the level of cytokines produced by peripheral blood mononuclear cells (PBMNC) in patients with aplastic anemia (AA) and determine their effect on normal bone marrow (BM) colony growth. Thirty-five patients with AA and 21 normal controls were enrolled in the study. Medium conditioned by PBMNC of AA patients in the presence of phytohemagglutinin (PHA) was found to be suppressive to the clonal growth of normal BM cells. Thus, we further determined the presence in the PBMNC conditioned medium (CM) of inhibitory cytokines (macrophage inflammatory protein-1 alpha [MIP-1 alpha], transforming growth factor-beta 2 [TGF-beta 2], interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha]) and stimulatory cytokines (granulocyte-macrophage colony-stimulatory factor [GM-CSF], interleukin-3 [IL-3], and stem cell factor [SCF]). The results show no significant difference between AA patients and normal controls in the spontaneous production of all cytokines by PBMNC. After PHA stimulation, the production of MIP-1 alpha, IFN-gamma, TNF-alpha, and GM-CSF significantly increased in the cultures of AA patients (p = 0.0009, 0.0002, 0.0022, and 0.0156, respectively). However, both TGF-beta 2 and SCF were undetectable in most of the tested samples. IL-3 was measured in the conditioned medium only after PHA stimulation, but without significant difference between the two groups (p = 0.67). Furthermore, the myelopoietic suppressing effect of AA-PBMNC CM could be significantly blocked by pretreatment with specific antibodies to the corresponding inhibitory cytokines (MIP-1 alpha, IFN-gamma, and TNF-alpha). After antibody neutralization, an apparent change occurred in the clonal growth of normal BM cells incubated with AA-PBMNC CM, resulting in colony enhancement of 205, 131, and 237% by anti-MIP-1 alpha, anti-IFN-gamma, and anti-TNF-alpha, respectively. These results suggest that overproduction of inhibitory cytokines, rather than underproduction of stimulating cytokines, may play a role in the progression of at least some patients with AA. SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/8536789/Production_of_hematopoietic_regulatory_cytokines_by_peripheral_blood_mononuclear_cells_in_patients_with_aplastic_anemia_ L2 - http://www.diseaseinfosearch.org/result/556 DB - PRIME DP - Unbound Medicine ER -