Receptor-selective IL-4 mutein modulates inflammatory vascular cell phenotypes and attenuates atherogenesis in apolipoprotein E-knockout mice.

  title={Receptor-selective IL-4 mutein modulates inflammatory vascular cell phenotypes and attenuates atherogenesis in apolipoprotein E-knockout mice.},
  author={Yanhui Lin and Zhiheng Chen and Seiya Kato},
  journal={Experimental and molecular pathology},
  volume={99 1},
The therapeutic potential of interleukin-4-mediated immunomodulation has not been proven in atherogenesis. Type I IL-4 receptor consists of IL-4Rα and a common γ chain, whereas type II IL-4R is a heterodimer of IL-4Rα and IL-13Rα1. Reportedly, the human IL-4 mutein IL-4/R121E is able to act as an IL-4RI-specific agonist. Here, we investigated the effect of receptor-specific IL-4 mutein on vascular cell phenotypes and atherogenesis. Initially, a plasmid expressing murine IL-4/Q116E, analogous to… 
Heterogeneity of atherosclerotic plaque macrophage origin, phenotype and functions: Implications for treatment
The advances in understanding of monocyte and macrophage heterogeneity and its implications for specific therapeutic interventions are described, aiming to reduce the ever growing significant risk of cardiovascular events without any detrimental side effects on the patient's immune response.
Immune-mediated mechanisms of atherosclerosis and implications for the clinic
The understanding of the role of the immune response in atherosclerosis is reviewed, focusing on the pathways currently amenable to therapeutic modulation, to help address and identify the appropriate settings where an immune pathway can be targeted with minimal risk.
Monocyte Chemoattractant Protein‐1 and Large Artery Structure and Function in Young Individuals: The African‐PREDICT Study
The authors found elevated central systolic blood pressure and MCP‐1 in young blacks, where cIMT was independently associated with MCP•1 in black women.
Expressions of serum inflammatory cytokines and their relationship with cerebral edema in patients with acute basal ganglia hemorrhage.
Serum levels of IL-4, IL-6 and IL-10 are positively correlated while theIL-10 level is negatively correlated with the severity of the cerebral edema in patients with acute basal ganglia hemorrhage.


An immune cell-selective interleukin 4 agonist.
  • A. Shanafelt, C. Forte, +4 authors J. Greve
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
IL-4/R121E exhibits a spectrum of activities in vitro that suggest utility in the treatment of certain autoimmune diseases, and contains the mutation Arg-121 to Glu, which is consistent with this observation.
Type I IL-4Rs Selectively Activate IRS-2 to Induce Target Gene Expression in Macrophages
H Heller et al. have found a critical difference in the signaling pathways activated by IL-4 and IL-13, which may help in the development of more selective therapies against allergic asthma.
Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4Rα, IL-13Rα1, and γc regulates relative cytokine sensitivity
It is shown that mouse bone marrow–derived macrophages and human and mouse monocytes showed a much greater sensitivity to IL-4 than to IL -13, and this provides an explanation for IL-13's principal function as an “effector” cytokine andIL-4's principal role as an“immunoregulatory” antibody.
Unique functions of the type II interleukin 4 receptor identified in mice lacking the interleukin 13 receptor α1 chain
Type I and II IL-4 receptors exert distinct effects on immune responses, and Il13ra1−/− mice showed much less mortality after infection with Schistosoma mansoni and much more susceptibility to Nippostrongylus brasiliensis.
Interleukin-4 Deficiency Decreases Atherosclerotic Lesion Formation in a Site-Specific Manner in Female LDL Receptor−/− Mice
In conclusion, IL-4 deficiency reduced atherosclerotic lesion formation in a site-specific manner in female LDL receptor−/− mice fed a high-fat diet.
A Murine IL-4 Receptor Antagonist That Inhibits IL-4- and IL-13-Induced Responses Prevents Antigen-Induced Airway Eosinophilia and Airway Hyperresponsiveness1
The therapeutic potential of IL- 4 mutant protein receptor antagonists that inhibit both IL-4 and IL-13 in the treatment of allergic asthma are demonstrated.
A Murine Interleukin-4 Antagonistic Mutant Protein Completely Inhibits Interleukin-4-induced Cell Proliferation, Differentiation, and Signal Transduction*
This double mutant of the murine IL-4 protein, both glutamine 116 and tyrosine 119 were substituted by aspartic acid residues resulted in the QY variant, a highly efficient antagonist for interleukin-4 (IL-4) in the mouse system.
Pitrakinra, a dual IL-4/IL-13 antagonist for the potential treatment of asthma and eczema.
  • S. Antoniu
  • Medicine
    Current opinion in investigational drugs
  • 2010
Pitrakinra demonstrated a potent inhibitory activity on IL-4/IL-13-mediated proliferative effects in vitro and reduced allergen-induced inflammation in animal models of asthma and skin inflammation.
Regulation of chemokine expression by antiinflammatory cytokines
Mechanisms through which IL-10 and IL-4 acttodampen inflammatory responses are mechanistically distinct and involve diverse intracellular signaling pathways.
Biochemical and morphological characterization of vascular and lymphocytic interleukin-4 receptors.
The demonstration of a vascular distribution pattern for the IL-4 receptor in addition to expression on lymphocytes suggests that vascular functional alterations, transduced through a unique IL-2 receptor complex (the type II IL-3 receptor), may be of importance during immunological and allergic inflammatory events.