Maryam Teimouri; Ahad Muhammadnejad; Mir Saeed Yekaninejad; Alireza Razavi; Gholam Ali Kardar
Abstract
Background: Interleukin-2 (IL-2) is a well-known cytokine that plays a crucial role in stimulating immune cells, including natural killer (NK) cells and cytotoxic T cells. It has been studied as an immunotherapy for a variety of diseases, including cancer. However, due to its short serum half-life, high ...
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Background: Interleukin-2 (IL-2) is a well-known cytokine that plays a crucial role in stimulating immune cells, including natural killer (NK) cells and cytotoxic T cells. It has been studied as an immunotherapy for a variety of diseases, including cancer. However, due to its short serum half-life, high doses of IL-2 are required which can result in systemic toxicities like capillary leak syndrome.Objective: To demonstrate the enhanced antitumor efficacy of Albumin Binding Domain-conjugated IL-2 (ABD-IL-2) at a lower dose compared to IL-2.Methods: IL-2 and ABD-IL-2 were purified using Ni-NTA resin with a histidine sequence added to their C-terminal region for purification purpose. Peripheral blood lymphocytes were stimulated with IL-2 and ABD-IL-2 to assess their function. 4T1 cells were injected into BALB/c mice to establish a breast cancer model with metastasis evaluated in the lungs.Results: Both recombinant proteins significantly stimulated T lymphocyte proliferation compared to the negative control (P=0.000, P=0.001). Administration of both proteins reduced the size of isolated tumors in the breast cancer mouse model. The control group had more nodules and larger lung metastatic centers (P=0.000). Metastasis to secondary lymphoid organs occurred only in the control group.Conclusion: By using ABD-IL-2 at a one-third concentration compared to IL-2, we aimed to reduce administration toxicity associated with high doses of IL-2 in immunotherapy. This approach shows potential for improving IL-2-based treatments while minimizing adverse effects.
Abolghasem Ajami; Farshideh Abedian; Seyyed Hamzeh Hosseini; Elahe Akbarian; Reza Alizadeh-Navaei; Mehrdad Taghipour
Volume 11, Issue 3 , September 2014, , Pages 200-209
Abstract
Background: Schizophrenia is a disorder of the executive function of both sensory and central nervous system. Recent studies suggest that immune mechanisms play a role in the pathophysiology of this disease. The variations in cytokine concentrations have been associated with psychopathology and treatment ...
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Background: Schizophrenia is a disorder of the executive function of both sensory and central nervous system. Recent studies suggest that immune mechanisms play a role in the pathophysiology of this disease. The variations in cytokine concentrations have been associated with psychopathology and treatment of schizophrenia. Objective: To investigate the changes in serum concentrations of TNF- α, IL-10, and IL-2 in schizophrenic patients before and 40 days after treatment. Methods: In a case-control study, 26 schizophrenic patients and 26 healthy individuals were enrolled as the control group. PANSS scale questionnaire was used for diagnosis and assessing the severity of the disease. All patients were then treated with risperidone or clozapine for 40 days. Serum concentrations of TNF- α, IL-10 and IL-2 were measured by ELISA before and after treatment in both groups. Paired t-test and Independent t-test were used for comparison of data. Results: Comparison of TNF-α and IL-10 concentrations in patients before and after treatment revealed a significance decrease of TNF- α and increase of IL-10 concentrations (p=0.002, and p=0.008, respectively). Serum concentrations of IL-2 were lower than the detection limit of assay and were not detectable. In comparison with healthy controls, serum concentrations of TNF- α in schizophrenic patients were higher, while IL-10 concentrations were lower before treatment although the differences were not significant (p=0.291 and p=0.375, respectively). There was no correlation between cytokine concentrations and the positive and negative scale (PANSS). Also no significant difference in the admission, relapses, and duration of illness before and after treatment was observed. Conclusions: Increase of TNF- α and decrease of IL-10 may have an important role inpsychopathology of schizophrenia.