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- Hansson, Markus, 1974, et al.
(författare)
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Histamine protects T cells and natural killer cells against oxidative stress.
- 1999
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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
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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.
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| 2. |
- Hellstrand, Kristoffer, 1956, et al.
(författare)
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Histamine and cytokine therapy.
- 1998
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Ingår i: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 37:4, s. 347-53
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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.
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