Functions of IL-4 and Control of Its Expression

Brown, Melissa A.; Hural, John

doi:10.1615/critrevimmunol.v17.i1.10

Cited by 287 publications

(139 citation statements)

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“…IL-4 is a pleiotropic cytokine produced by activated helper T cells which exerts multiple biological effects through binding to specific receptors on the cell surface (Mire-Sluis 1998; Nelms et al 1999). Although IL-4 has initially been described as a B cell growth factor (Farrar et al 1983), it has since been reported to regulate a wide range of immune responses, including increases in proliferation of B and T cells, enhancement of IgE synthesis, and up-regulation of the expression of class I and II HLA antigens (for reviews see Brown and Hural 1997;Paul 1991). IL-4 exerts its effects on cells of different lineages such as fibroblasts, endothelial cells (Lowenthal et al 1988), microglia (Chao et al 1993) and astrocytes (Brodie and Goldreich 1994;.…”

Section: Discussionmentioning

confidence: 99%

“…In accordance with the observation of potentiating effects of IL-4 on LPS-induced sickness behavior, the results of a few reports indicate that IL-4 can exert pro-inflammatory effects. In vivo studies have demonstrated both positive and negative effects on the outcome of infectious diseases (Brown and Hural 1997;Jain-Vora et al 1998). In particular, sublethally infected mice given IL-4 at the time of infection responded to this treatment with increased mortality and overproduction of TNF-␣ (Giampietri et al 2000).…”

Section: Discussionmentioning

confidence: 99%

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Dual Effect of Central Injection of Recombinant Rat Interleukin-4 on Lipopolysaccharide-Induced Sickness Behavior in Rats

Bluthé

Lestage

Rees

et al. 2002

Neuropsychopharmacology

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Systemic administration of the bacterial endotoxin lipopolysaccharide (LPS) has profound depressive effects on behavior that are mediated by the inducible expression of pro-inflammatory cytokines, such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor ␣ (TNF), in the brain. To assess the regulatory effects of the anti-inflammatory cytokine IL-4 on LPS-induced sickness behavior, rats injected intra-peritoneally (i.p.) with LPS were administered intracerebroventricularly (i.c.v.) with When an organism becomes sick during the course of an infection, several changes occur, which are mediated by the central nervous system (CNS). These changes include regulated increases in body temperature, sleep, activation of the hypothalamo-pituitary-adrenocortical (HPA) axis, decreases in locomotor activity, feeding, drinking, and social interactions, and alterations in brain neurotransmitters. They are due to the release of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-␣ ) by activated monocytes and macrophages Dinarello 2000;Gabay and Kushner 1999;Krueger et al. 1999;Mulla and Buckingham 1999;Rothwell 1997;Turrin and Plata-Salaman 2000). The same effects can be obtained by systemic administration of the cytokine-inducer lipopolysaccharide (LPS), a component of the cell wall of Gram-negative bacteria (Cabrera et al. 2000;Francis et al. 2000;Lacosta et al. 1999;Ma et al. 2000;MohanKumar et al. 2000;Roth and de Souza 2001;Swiergel and Dunn 1999;Yirmiya 1996;Yirmiya et al. 2001). Peripherally released cytokines act on the brain by inducing the expression and release of cytokines in the central nervous system (Eriksson et al. 2000;Konsman et al. 1999;Layé et al. 2000;Quan et al. 2000). LPS induces the expression of not only pro-inflammatory but also anti-inflammatory cytokines such as IL-10 and IL-13 in the brain (Wong et al. 1997 Laman et al. 1998;Liedtke et al. 1998; Woodroofe and Cuzner 1993). Anti-inflammatory cytokines have the ability to suppress the synthesis of IL-1, TNF, and other cytokines in peripheral immune and non-immune cells (Dinarello 1997;Marie and Cavaillon 1997).There has been a recent surge of interest in the behavioral effects of cytokines in neuropsychopharmacology. Several reasons account for that, including the fact that cytokine-induced sickness behavior is not the result of weakness and physical debilitation but appears to be the expression of a previously unrecognized motivational state that is triggered by peripheral immune stimuli and reorganizes the organism's priorities (Dantzer 2001). In addition, the possibility of an intersection between sickness behavior and depression has raised new and important issues in psychopathology.If sickness behavior is the ineluctable result of the brain action of those proinflammatory cytokines that are released at the periphery during the course of an innate immune response or even in response to exteroceptive stressors, it becomes important to find out how this behavior is regulated. The production and ac...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dual Effect of Central Injection of Recombinant Rat Interleukin-4 on Lipopolysaccharide-Induced Sickness Behavior in Rats

Bluthé

Lestage

Rees

et al. 2002

Neuropsychopharmacology

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“…IL-4 release is important in promoting Th2-mediated allergic immune responses. 8,9 The action of IL-4 is not limited to the initiation of Th2 responses but may also stimulate other cellular responses that contribute to the manifestations of allergic disease. 8 Potential cellular sources of IL-4 include CD4 þ T cells, 9 mast cells, 10 basophils, 11 NK1.1 þ T cells, 12 gdT cells 13 and eosinophils.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 The action of IL-4 is not limited to the initiation of Th2 responses but may also stimulate other cellular responses that contribute to the manifestations of allergic disease. 8 Potential cellular sources of IL-4 include CD4 þ T cells, 9 mast cells, 10 basophils, 11 NK1.1 þ T cells, 12 gdT cells 13 and eosinophils. 14 These findings suggest that inhibition of the action of IL-4 may be particularly helpful in suppression of allergic reaction, in which IL-4 is responsible for the differentiation of allergen-specific Th2 cells.…”

Section: Introductionmentioning

confidence: 99%

A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma

et al. 2003

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Interleukin 4 (IL-4) is essential for the switching of B cells to IgE antibody production and for the maturation of T helper (Th) cells toward the Th2 phenotype. These mechanisms are thought to play a crucial role in the pathogenesis of the allergic airway inflammation observed in asthma. In the present study, we examined the anti-inflammatory effects of DNA administration of murine IL-4 mutant Q116D/Y119D (IL-4 double mutant, IL-4DM), which binds to the IL-4 receptor a and is an antagonist for IL-4. Immunization of BALB/c mice with alum-adsorbed ovalbumin (OVA) followed by aspiration with aerosolized OVA resulted in the development of allergic airway inflammation. A single administration of IL-4DM DNA before the aerosolized OVA challenge protected the mice from the subsequent induction of allergic airway inflammation. Serum IgE level and extent of eosinophil infiltration in bronchoalveolar lavage (BAL) from IL-4DM DNA-administered mice were significantly lower than those in BAL from control plasmid-immunized mice. In our study, IL-4 or IL-4 mutants were not detected in sera from mice that had received a single administration of IL-4DM DNA. The results of this study provide evidence for the potential utility of IL-4 mutant antagonist DNA inoculation as an approach to gene therapy for asthma.

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“…IL-4 contributes to the polarization toward Th2 differentiation and promotes IgE class switching (6,7). The actions of IL-4 are not limited to the initiation of Th2 responses, but also may stimulate other cellular responses that contribute to manifestations of allergic diseases (6).…”

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confidence: 99%

Cutting Edge: Eotaxin Elicits Rapid Vesicular Transport-Mediated Release of Preformed IL-4 from Human Eosinophils

Bandeira‐Melo

Sugiyama

Woods

et al. 2001

The Journal of Immunology

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IL-4 release is important in promoting Th2-mediated allergic and parasitic immune responses. Although human eosinophils are potential sources of IL-4, physiologic mechanisms to elicit its release have not been established. By flow cytometry and microscopy, eosinophils from normal donors uniformly contained preformed IL-4. In contrast to cytolytic IL-4 release from calcium ionophore-activated eosinophils, eotaxin and RANTES, but not IFN-γ, elicited IL-4 release by noncytotoxic mechanisms. With a dual Ab capture and detection immunofluorescent microscopic assay, IL-4 was released at discrete cell surface sites. IL-5 enhanced eotaxin-induced IL-4 release, which was mediated by G protein-coupled CCR3 receptors, detectable as early as 5 min and maximum within 1 h. IL-4 release was not diminished by transcription or protein synthesis inhibitors, but was suppressed by brefeldin A, an inhibitor of vesicle formation. Thus, CCR3-mediated signaling can rapidly mobilize IL-4 stored preformed in human eosinophils for release by vesicular transport to contribute to immune responses.

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Functions of IL-4 and Control of Its Expression

Cited by 287 publications

References 0 publications

Dual Effect of Central Injection of Recombinant Rat Interleukin-4 on Lipopolysaccharide-Induced Sickness Behavior in Rats

Dual Effect of Central Injection of Recombinant Rat Interleukin-4 on Lipopolysaccharide-Induced Sickness Behavior in Rats

A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma

Cutting Edge: Eotaxin Elicits Rapid Vesicular Transport-Mediated Release of Preformed IL-4 from Human Eosinophils

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