Pulmonary reactions to novel chemotherapeutic agents and biomolecules
Philippe Camus, Edward C Rosenow in Drug-induced and Iatrogenic Respiratory Disease, 2010
Interleukin-2 (IL-2) is an endogenous cytokine that is produced by activated T-cells and natural killer cells and has direct activating effects on several subsets of immune cells.25 In its recombinant form, it is used as an immunoactivating cancer treatment for metastatic melanoma and renal cell carcinoma, but its clinical utility has been limited by the development of a vascular leak syndrome.26 Increased microvascular permeability results in weight gain, peripheral oedema, oliguria and non-cardiogenic pulmonary oedema. This presents within a few days after IL-2 administration as a subacute clinical syndrome characterized by dyspnoea, cough and hypoxaemia. Radiographic imaging demonstrates pleuropulmonary abnormalities in approximately 75 per cent of patients, with the most common findings being bilateral perihilar alveolar or interstitial infiltrates and pleural effusions.27
Tuberculosis Clinical Immunology
Peter D O Davies, Stephen B Gordon, Geraint Davies in Clinical Tuberculosis, 2014
IFNγ 200 μg given thrice weekly for four months by aerosol or by subcutaneous injection versus standard therapy alone in a total of 89 patients with drug-sensitive pulmonary TB [59]. There was no effect of either adjunctive treatment on sputum culture conversion or on high-resolution chest computed tomography. A study conducted by Intermune compared aerosolised IFNγ 500 μg thrice weekly versus placebo for six months in a total of 80 patients with multidrug-resistant TB (MDR-TB), all of whom also received standardised therapy with second-line drugs [60]. The study was halted prematurely by its external monitoring board due to a trend towards increased mortality in the experimental arm (10 deaths, vs. 5 in controls, P = 0.14), with no effect on sputum culture or chest radiography. The study findings have never been published. Several other studies with fewer than 10 subjects per arm in which adjunctive IFNγ or IFNα was given by aerosol or subcutaneous injection have reported inconsistent results [61–65]. These clinical findings mirror the lack of consistent effect of added IFNγ on intracellular M. tuberculosis using in vitro models. One additional study examined the effects of interleukin-2 (IL-2), a cytokine that promotes T-cell proliferation and differentiation. Adjunctive IL-2 (225,000 IU) given subcutaneously twice daily for one month versus placebo in 110 patients with drug-sensitive TB tended to delay rather than enhance sputum culture conversion [66].
Bacterial infections after lung transplantation
Wickii T. Vigneswaran, Edward R. Garrity, John A. Odell in LUNG Transplantation, 2016
Innate immune effector cells are important in host defense against bacterial pathogens. Immune suppression is associated with a decrease in certain macrophage functions that are part of the innate immune response to infection. Immune suppression to prevent rejection and BOS reduce proinflammatory and Th1 cytokines, which are important in host defense against bacterial infection. Some have proposed monitoring levels of these cytokines to help avoid excessive immunosuppression in stable lung transplant patients. A number of studies of cells collected by bronchoalveolar lavage (BAL) have shown that the T cells of patients with infection demonstrate lower intracellular cytokine production than do those of patients without infection.20 Interleukin-2 [IL-2] production by CD4+ T cells and production of tumor necrosis factor a by CD8+ T cells decreased after stimulation.
Simlukafusp alfa (FAP-IL2v) immunocytokine is a versatile combination partner for cancer immunotherapy
Published in mAbs, 2021
Inja Waldhauer, Valeria Gonzalez-Nicolini, Anne Freimoser-Grundschober, Tapan K Nayak, Linda Fahrni, Ralf J. Hosse, Danny Gerrits, Edwin J. W. Geven, Johannes Sam, Sabine Lang, Esther Bommer, Virginie Steinhart, Elisabeth Husar, Sara Colombetti, Erwin Van Puijenbroek, Markus Neubauer, J. Mark Cline, Pradeep K. Garg, Gregory Dugan, Federica Cavallo, Gonzalo Acuna, Jehad Charo, Volker Teichgräber, Stefan Evers, Otto C. Boerman, Marina Bacac, Ekkehard Moessner, Pablo Umaña, Christian Klein
Interleukin-2 (IL-2) is a cytokine produced primarily by activated T cells that plays a critical function in the generation, differentiation, survival, and homeostasis of immune effector cells.1,2 IL-2 signaling is mediated by binding to the IL-2 receptor (IL-2 R), which consists of up to three individual subunits, α (CD25), β (CD122), and γ (CD132).1 The low-affinity dimeric IL-2 Rβγ form is expressed on natural killer (NK) cells, monocytes, macrophages, and resting CD4+ and CD8+ T cells.1,2 The high-affinity trimeric IL-2 Rαβγ is transiently induced on activated NK cells and CD4+ and CD8+ T cells. IL-2 functions to expand T cell populations in an autocrine fashion, differentiate antigen-activated CD4+/CD8+ T cells into effector T cell subsets, and activate NK cells.2 Activation of innate and adaptive immune effector cells in this manner is the basis for using IL-2 to stimulate an anti-tumor response.3–5 However, to counteract autoimmunity, IL-2 also has immunosuppressive properties and is involved in peripheral immune tolerance mediated by CD4+ FOXP3+ regulatory T cells (Tregs), which constitutively express high levels of IL-2 Rα.2,6,7 Tregs suppress T cell activity, thereby compromising anti-tumor immunity.8 IL-2 is also essential for activation-induced cell death (AICD) of activated T cells by upregulating the expression of Fas ligand and downregulating apoptosis inhibitors.9,10
Abnormalities of quantities and functions of CD56bright natural killer cells in non-severe aplastic Anemia
Published in Hematology, 2019
Yang Li, Shaoxue Ding, Chunyan Liu, Tong Chen, Hui Liu, Lijuan Li, Zonghong Shao, Rong Fu
Interleukin 2 (IL-2) is a T cell growth factor that has been shown to modulate several in vitro immune responses. Hefeneider [25] found that administration of purified IL-2 to naive, non-antigen-challenged recipients resulted in substantial potentiation of NK cell activity. Fehniger [26] demonstrated that CD56bright NK cells endogenous T cell-derived IL-2, acting through the NK high-affinity IL-2 receptor, costimulating CD56 bright NK cells to secrete IFN-γ. IL-18 is a newly discovered proinflammatory cytokine, which activates NK cells closely related to its dose [27]. Shan found that the level of the IL-18 in the serum of AA was higher than that in NSAA and normal controls, the serious the disease, the higher the IL-18 [28]. Takeda [29] demonstrated that the importance of in vivo of IL-18 in NK lytic activity cell activity. Our result showed that IL-2 and IL-18 in the newly diagnosed NSAA group and the remission group were higher than that of the normal control group. A recent study showed that the effect of CD56bright NK cells in bacterial infections was demonstrated in vitro which in synergy with IL-2, exposure of NK cells to bacterial proteins through TLRs induces CD56bright NK cells to produce IFN-γ [30]. In our experiment, increased IL-2 may activate CD56 bright NK cells produced more granzyme B and promote the activation of the immune mechanism.
Treatment of inflammatory complications in common variable immunodeficiency (CVID): current concepts and future perspectives
Published in Expert Review of Clinical Immunology, 2023
T cells in CVID are not only activated, they are also exhausted, as indicated in a study from our group where patients with GLILD had high levels of soluble CD25, IFN-gamma and TNF, but also of the T-cell exhaustion marker soluble TIM3 [127]. Exhausted T cells have low proliferative capacity, a consistent feature of CVID that has been known for decades, and with some studies presenting therapeutic measures to enhance the proliferative potential of T cells. Our group showed in the late 90ties that the low proliferation of T cells in CVID could be partially reversed by inhibitors of cyclic AMP in vitro [128]. Interleukin-2 (IL-2) is a strong inducer of T-cell growth and proliferation. Cunningham-Rundles and her colleagues tried giving CVID-patients low dose interleukin-2 and showed not only that T cells from patients improved their proliferative capacity, but that there also was an increase in immunoglobulin levels [129].
Related Knowledge Centers
- Interleukin
- Protein
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- Immune System
- Lymphocyte
- Infection
- Cytokine
- Immune Response
- Il-2 Receptor