Interleukin-2 (IL-2), the first cloned cytokine, is a multifunctional molecule with diverse cellular origins. As a pivotal T-cell growth factor, IL-2 is crucial for T-cell proliferation and the generation of effector and memory cells. Besides, IL-2 and its receptor (IL-2R) are expressed in various cell types within the brain and have been implicated in the pathogenesis of several neurological disorders. In conditions characterized by primary or secondary inflammatory processes, such as multiple sclerosis, Alzheimer's disease, ischemic stroke, and encephalitis, IL-2/IL-2R expression exhibits region- and subtype-specific and variations associated with disease stages in plasma, cerebrospinal fluid (CSF), and brain tissues. These variations highlight the potential of IL-2/IL-2R as promising diagnostic and prognostic biomarkers, as well as therapeutic targets. This review provides a comprehensive summary of the roles, expression patterns, and regulatory mechanisms of IL-2/IL-2R in immune-mediated disorders of the central nervous system (CNS), with particular emphasis on the impact of genetic polymorphisms in IL-2 and IL-2R subunits on disease susceptibility and progression. In addition, the research advances in IL-2/IL-2R-targeted therapies are also discussed, offering novel insights into the immunotherapeutic strategies for CNS diseases.

01 Mar 2025·Journal of Clinical Laboratory Analysis

The Diagnostic Value of Interleukin‐2 and Interferon‐γ Induced by Fusion Protein (ESAT‐6/CFP‐10/Rv1985c) for Active Mycobacterium tuberculosis Infection

Article

Author: Lin, Minggui ; Li, Xiaochen ; Zhao, Xiuying ; Zhao, Zhipeng ; Wei, Qian ; Li, Runqing ; Wang, Yujie ; Xiong, Pan

ABSTRACTObjectiveThis study aimed to evaluate the diagnostic ability of interleukin 2 (IL‐2) and interferon gamma (IFN‐γ) release assay induced by the fusion protein (ESAT‐6/CFP‐10/Rv1985c) for detecting active tuberculosis (ATB) in clinically visiting patients.MethodsA total of 970 subjects (215 in ATB group and 755 in non‐ATB group) underwent both an interferon‐γ release assay (IGRA) and a TB‐DNA PCR assay. Using clinical diagnosis as the gold standard, both qualitative and quantitative test results for IL‐2 and IFN‐γ were analyzed. Subsequently, the diagnostic ability of IL‐2 and IFN‐γ to screen for ATB among the high‐risk population was then evaluated.ResultsIL‐2 exhibited higher specificity, while IFN‐γ demonstrated higher sensitivity in distinguishing between ATB and non‐ATB subjects. The sensitivity of the serial application of IL‐2 and IFN‐γ had no significant difference (p = 1.000) compared with IFN‐γ; the specificity of the serial application of IL‐2 and IFN‐γ had no significant difference (p = 0.708) compared with IL‐2. Quantitative analysis of the results revealed that the IL‐2 and IFN‐γ values were significantly higher in the ATB group compared with the non‐ATB group. Additionally, the combined predictors of IL‐2 and IFN‐γ did not show a significant difference compared with IL‐2 alone (p = 0.324) or IFN‐γ alone (p = 0.405).ConclusionsThis study demonstrated that IL‐2 and IFN‐γ release assays induced by the fusion protein (ESAT‐6/CFP‐10/Rv1985c) were valuable for distinguishing ATB from non‐ATB subjects, with IL‐2 exhibiting higher specificity and IFN‐γ demonstrating higher sensitivity.

01 Feb 2025·Journal of Allergy and Clinical Immunology

Low-dose IL-2 in birch pollen allergy: A phase-2 randomized double-blind placebo-controlled trial

Article

Author: Rosenzwajg, Michelle ; Domis, Nathalie ; Lorenzon, Roberta ; Gherasim, Alina ; Bellier, Bertrand ; Vicaut, E. ; Soria, Angele ; de Blay, Frederic ; Beck, Marine ; Dietsch, Franck ; Klatzmann, David ; Vicaut, Eric ; De Blay, Frederic ; Chantran, Yannick

BACKGROUNDRegulatory T (Treg) cells are pivotal in immune tolerance to allergens. Low-dose IL-2 (IL-2_LD) activates Treg cells.OBJECTIVEOur aim was to assess IL-2_LD efficacy for controlling clinical responses to allergen exposures.METHODSRHINIL-2 was a phase-2a, randomized, double-blind, placebo-controlled trial. Patients with allergic rhinitis to birch pollen (BP) were included; 66% of them had concomitant asthma. All had a total nasal symptom score (TNSS) of 5 or more following nasal exposure to BP in an environmental exposure chamber. Patients received 1 MUI per day of IL-2 (n = 12) or placebo (n = 12) for 5 days, followed by weekly injections for 4 weeks. Clinical responses to subsequent BP exposures in the environmental exposure chamber were evaluated by using TNSS, the rhinitis visual analog scale (VAS), and spirometry. The primary efficacy end point was the difference in TNSS area under the curve (AUC) between inclusion and day 40.RESULTSIL-2_LD treatment induced a significant expansion of Treg cells. The difference in TNSS AUC between inclusion and day 40 AUC in the IL-2 and placebo groups was not significant. TNSS and visual analog scale AUCs were significantly reduced from baseline to day 40 in the IL-2_LD group only (P = .04 and P = .01, respectively). The ratio of FEV₁ to forced vital capacity (FEV_1P) and the forced midexpiratory flow (FEF_25%-75%) showed improvement in the IL-2_LD-treated versus in the groups given placebo at day 40 (P = .04 and P = .04, respectively). However, the short treatment duration used in this study could not have effects on specific IgE or IgG4 levels given their half-life. There were no severe treatment-related adverse events.CONCLUSIONIL-2_LD is well tolerated in patients with allergy, even in those with asthma, thus clearing the path for further therapeutic development. Our work suggests that Treg cells can safely attenuate an ongoing allergic response. It paves the way for larger studies with longer treatment periods, which are needed to properly evaluate the therapeutic potential of IL-2 in allergy.

100 Deals associated with Interleukin-2(Amgen, Inc.)

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-	Interleukin-2(Amgen, Inc.)	L03AC01	-

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Indication	Country/Location	Organization	Date
Hepatitis B	-	Amgen, Inc.	-
Neoplasms	-	Amgen, Inc.	-

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