| 1. |
- Hansson, Markus, 1974, et al.
(författare)
-
Histamine protects T cells and natural killer cells against oxidative stress.
- 1999
-
Ingår i: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. - 1079-9907. ; 19:10, s. 1135-44
-
Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress inflicted by monocytes/macrophages (MO) is recognized as an important immunosuppressive mechanism in human neoplastic disease. We report that two types of lymphocytes of relevance for protection against malignant cells, T cells and natural killer (NK) cells, became anergic to the T cell and NK cell activator interleukin-2 (IL-2) after exposure to MO-derived reactive oxygen metabolites and subsequently acquired features characteristic of apoptosis. The MO-induced anergy and apoptosis in T cells and NK cells were reversed by histamine, an inhibitor of reactive oxygen metabolite synthesis in MO. We propose that strategies to circumvent oxidative inhibition of lymphocytes may be of benefit in immunotherapy of neoplastic disease.
|
|
| 2. |
- Hellstrand, Kristoffer, 1956, et al.
(författare)
-
Histamine and cytokine therapy.
- 1998
-
Ingår i: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 37:4, s. 347-53
-
Tidskriftsartikel (refereegranskat)abstract
- Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) are potent activators of natural killer (NK) cells and other anti-tumor effector cells, but the results obtained in clinical trials with these cytokines have proved disappointing in many forms of cancer. It may be that IL-2 and IFN-alpha are often not sufficiently effective because intratumoral monocytes/macrophages (MO) inhibit the cytokine-induced activation of cytotoxic effector lymphocytes such as NK-cells at the site of tumor growth. An essential part of this inhibitory signal is conveyed by MO-derived reactive oxygen species (ROS), which potently inhibit NK-cell-related functions, including the constitutive and cytokine-induced cytotoxicity against tumor cells. Histamine, a biogenic amine, inhibits ROS formation in MO; thereby, histamine synergizes with IL-2 and with IFN-alpha to induce killing of NK-cell-sensitive human tumor cells in vitro. Furthermore, treatment of tumor-bearing mice with histamine potentiates cytokine-induced killing of NK-cell-sensitive murine tumor cells in vivo. In ongoing clinical trials, histamine has been added to IL-2 or IFN-alpha in immunotherapy of human neoplastic disease. The results of two pilot trials in metastatic melanoma suggest that the addition of histamine to IL-2/IFN-alpha prolongs survival time and induces regression of tumors, such as liver melanoma, which are considered refractory to immunotherapy with IL-2 or IFN-alpha. In acute myelogenous leukemia (AML), histamine and IL-2 have been given in order to protect patients in remission against relapse of leukemic disease. The potential benefit of histamine therapy in melanoma and AML will be evaluated in randomized trials.
|
|
| 3. |
|
|
| 4. |
- Hou, M, et al.
(författare)
-
Impact of endogenous thrombopoietin levels on the differential diagnosis of essential thrombocythaemia and reactive thrombocytosis.
- 1998
-
Ingår i: European journal of haematology. - 0902-4441. ; 61:2, s. 119-22
-
Tidskriftsartikel (refereegranskat)abstract
- By using the newly commercialized Quantikine human TPO immunoassay, plasma thrombopoietin (TPO) concentrations were measured in 12 patients with essential thrombocythaemia (ET), 13 patients with reactive thrombocytosis (RT) and 11 healthy volunteers. For the healthy volunteers the mean plasma TPO concentration was 21.1+/-11.0 pg/ml. The mean plasma TPO concentration in the group of RT was slightly lower (16.4+/-8.6 pg/ml) but did not differ significantly from the control group. The mean plasma TPO concentration in ET patients (44.1+/-45.2 pg/ml) was significantly (p<0.05) higher than the mean for RT patients, but did not differ statistically from the mean of healthy volunteers. These data suggest a defective clearance of plasma TPO in patients with ET.
|
|
| 5. |
- Hou, M, et al.
(författare)
-
Plasma thrombopoietin levels in thrombocytopenic states: implication for a regulatory role of bone marrow megakaryocytes.
- 1998
-
Ingår i: British journal of haematology. - 0007-1048. ; 101:3, s. 420-4
-
Tidskriftsartikel (refereegranskat)abstract
- To evaluate the diagnostic value of thrombopoietin (TPO, c-mpl ligand) measurements, and clarify the regulatory mechanisms of TPO in normal and in thrombocytopenic conditions, the plasma TPO concentration was determined in normal individuals (n = 20), umbilical cord blood (n = 40), chronic idiopathic thrombocytopenic purpura (ITP; n = 16), in severe aplastic anaemia (SAA; n = 3), chemotherapy-induced bone marrow hypoplasia (n = 10), myelodysplastic syndrome (MDS; n = 11), and sequentially during peripheral blood progenitor cell transplantation (n = 7). A commercially available ELISA and EDTA-plasma samples were used for the analysis. The plasma TPO concentration in the normals and umbilical cord blood were 52 +/- 12 pg/ml and 66 +/- 12 pg/ml, respectively. The corresponding values in patients with SAA and chemotherapy-induced bone marrow hypoplasia were 1514 +/- 336 pg/ml and 1950 +/- 1684 pg/ml, respectively, and the TPO concentration, measured sequentially after myeloablative chemotherapy and peripheral blood progenitor cell transplantation, was inversely related to the platelet count. In contrast, the plasma TPO recorded in patients with ITP (64 +/- 20 pg/ml) and MDS (68 +/- 23 pg/ml) were only slightly higher than normal levels. In conclusion, TPO levels were significantly elevated in patients in which bone marrow megakaryocytes and platelets in circulation were markedly reduced, whereas TPO levels were normal in ITP patients, and only slightly increased in the MDS patients. These latter patients displayed a preserved number of megakaryocytes in bone marrow biopsies. Our data support the suggestion that megakaryocyte mass affects the plasma TPO concentration. In thrombocytopenic patients a substantially increased plasma TPO implies deficient megakaryocyte numbers. However, TPO measurements do not distinguish between ITP and thrombocytopenia due to dysmegakaryopoiesis, as seen in MDS patients.
|
|
