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Lymphokine-activated killer induction and its regulation by macrophages in malignant pleural effusions
1Third Department of Internal Medicine, University of Tokushima School of Medicine.
Abstract:
Mononuclear cells (MNC) from pleural effusions and peripheral blood of 18 patients with primary lung cancer with malignant pleural effusion were studied. Pleural and blood MNC generated lymphokine-activated killer (LAK) activity similarly when cultured for 4 days with an optimal concentration of interleukin 2 (IL-2). Highly purified lymphocytes (greater than 98%) and monocyte-macrophages (greater than 90%) were isolated by discontinuous Percoll gradient centrifugation from pleural and blood MNC. Pleural macrophages, as well as blood monocytes, showed significant augmenting effects on in vitro LAK cell induction from pleural and blood lymphocytes by IL-2. During daily intrapleural administration of IL-2, significant induction of LAK activity in vivo was observed after 3 days, but then this LAK activity in pleural MNC decreased almost to zero by day 15. Daily injections of IL-2 resulted in reduction in the up-regulation of LAK induction by pleural macrophages and also in increases in the levels of soluble IL-2 receptors in pleural effusions. These findings indicate that in vivo LAK induction of lymphocytes in malignant effusions by IL-2 may be regulated by macrophages in the effusions.
Insights
Mononuclear cells from lung cancer patients showed similar lymphokine-activated killer (LAK) activity. Macrophages in pleural effusions may regulate in vivo LAK cell induction by interleukin-2 (IL-2).
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Malignant pleural effusions in lung cancer patients present unique cellular environments.
- Understanding immune cell function within these effusions is crucial for developing novel therapies.
Purpose of the Study:
- To investigate the in vitro and in vivo induction of lymphokine-activated killer (LAK) cell activity in mononuclear cells (MNC) from patients with primary lung cancer and malignant pleural effusion.
- To determine the role of pleural macrophages in modulating LAK cell generation.
Main Methods:
- Isolation of lymphocytes and monocyte-macrophages from pleural effusions and peripheral blood using Percoll gradient centrifugation.
- Assessment of LAK activity after in vitro culture with interleukin-2 (IL-2).
- Evaluation of in vivo LAK activity following intrapleural IL-2 administration and measurement of soluble IL-2 receptors.
Main Results:
- Pleural and blood MNC exhibited similar LAK activity upon IL-2 stimulation in vitro.
- Both pleural macrophages and blood monocytes augmented in vitro LAK induction.
- In vivo intrapleural IL-2 administration initially induced LAK activity, which subsequently declined, accompanied by reduced macrophage augmentation and increased soluble IL-2 receptors.
Conclusions:
- In vitro LAK cell generation is supported by both pleural macrophages and blood monocytes.
- In vivo LAK induction in malignant pleural effusions by IL-2 may be negatively regulated by pleural macrophages.
- Soluble IL-2 receptor levels may indicate altered immune responses within the pleural space during IL-2 therapy.
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