Disease relevance of Il4

• Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration by T cells and eosinophils, and expression of the cytokines IL-4, IL-5, and IFN-gamma [1].
• METHODS: Rats received an adenovirus producing IL-4 (AxCAIL-4), a control virus without insert, or control vehicle (phosphate buffered saline) intraarticularly before arthritis onset [2].
• In this study, we used a gene therapy approach to investigate the role of IL-4 in angiogenesis in rat adjuvant-induced arthritis (AIA), a model for rheumatoid arthritis [2].
• Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells [3].
• Interleukin 4 (IL-4) and IL-5 are essential for IgE production and eosinophilia, respectively, and are produced by mast cells in allergic conditions, for which glucocorticoids are widely used therapeutically [4].

High impact information on Il4

• Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor beta and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4(+)CD45RC- cells and CD4(+)CD8(-) thymocytes [5].
• The immunological basis for atopy is currently ascribed to an inherent bias in the CD4+ T cell response to nonreplicating antigens presented at mucosal surfaces, resulting in dominance of the T helper 2 (Th2) interleukin 4 (IL-4)-producing phenotype, which favors IgE production [6].
• In MBP plus LPS orally tolerized animals, in addition to upregulation of TGF-beta and reduction of inflammatory cytokines, there was enhanced expression of IL-4 and PGE2, presumably secondary to activation of an additional population of immunoregulatory cells [7].
• Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain [7].
• Glucocorticoids induce the expression of CD8 alpha chains on concanavalin A-activated rat CD4+ T cells: induction is inhibited by rat recombinant interleukin 4 [8].

Chemical compound and disease context of Il4

• Effect of allergen-specific immunotherapy on interleukin-4, interleukin-5 and interferon-gamma mRNA expression in the nasal mucosa of rats with allergic rhinitis [9].
• It may be concluded that the decreased expression of IL-4 and TGF-beta1 may be associated with decreased hydroxyproline synthesis, which then results in decreased lung fibrosis [10].
• Protective effect of Rolipram in experimental autoimmune neuritis: protection is associated with down-regulation of IFN-gamma and inflammatory chemokines as well as up-regulation of IL-4 in peripheral nervous system [11].
• Regulation of found in inflammatory zone 1 expression in bleomycin-induced lung fibrosis: role of IL-4/IL-13 and mediation via STAT-6 [12].
• Dexamethasone inhibits the anti-tumor effect of interleukin 4 on rat experimental gliomas [13].

Biological context of Il4

• Adenoviral vectors encoding rat IL-10 (AdIL-10), rat IL-4 (AdIL-4) or beta-galactosidase (AdlacZ) or without transgene (Addl324) were injected directly into rat hearts at the time of transplantation in order to test their potential to prolong heart allograft survival [14].
• We show pronounced up-regulation of IL-4 and more modest up-regulation of IFN-gamma in BN rats, but no up-regulation of either in LEW rats [15].
• We have previously shown, by fully quantitative polymerase chain reaction (PCR), up-regulation of interleukin-4 (IL-4) gene expression in HgCl2-treated BN rats, implicating Th2 cells in the autoimmune syndrome [15].
• Although the immunotherapy significantly decreased nasal airway resistance, dye leakage and histamine content in nasal irrigation after allergen challenge, no significant difference was found in IL-4 and IL-5 mRNA expression or in specific IgE level among the three groups [9].
• Our study shows that DP is associated with a decreased Th1 phenotype and IL-4 mRNA expression in the pancreas and spleen, and an n-3 PUFA diet upregulates Th2 profile [16].

Anatomical context of Il4

• Sensitized skin from IL-4(-/-) mice displayed normal thickening of the skin layers but had a drastic reduction in eosinophils and a significant increase in infiltrating T cells [1].
• Adenoviruses encoding IL-4 (AdIL-4) or IL-10 (AdIL-10) were administered to rats through the portal vein and the anti-adenovirus immune response was studied [17].
• T-helper subset 2 (Th2) lymphocytes produce interleukin 4 (IL-4) and IL-10, which exert anti-inflammatory actions on monocytes and macrophages [18].
• Absorption experiments demonstrated that when BCGF activity was absorbed out by large, activated human B cells, astrocyte-stimulatory activity was also depleted [19].
• Rat astrocytes were able to partially absorb out both BCGF and astrocyte-stimulatory activity [19].

Associations of Il4 with chemical compounds

• CONCLUSION: In rat AIA, IL-4 reduces synovial tissue vascularization via angiostatic effects, mediates inhibition of angiogenesis via an association with altered pro- and antiangiogenic cytokines, and may inhibit VEGF-mediated angiogenesis and exert its angiostatic role in part via alphavbeta3 integrin [2].
• Furthermore, the treatment with pioglitazone decreased the expression levels of proinflamatory cytokine (TNF alpha and IL-1beta) genes and Th1 cytokine (IFN-gamma) genes, and increased the expression levels of Th2 cytokine (IL-4) gene [20].
• Over several experiments, with or without IL-4 and/or IFN-gamma, serotonin release correlated inversely with nitrite production [21].
• Purified rat splenic CD8+ T cells were cultured for 6 days with PMA, ionomycin and IL-2 with or without IL-4 or anti-IFN-gamma and restimulated with PMA and ionomycin [22].
• Reciprocal effects of interleukin-4 and interferon-gamma on immunoglobulin E-mediated mast cell degranulation: a role for nitric oxide but not peroxynitrite or cyclic guanosine monophosphate [21].

Regulatory relationships of Il4

• In situ hybridization showed that cells expressing IL-4 and -5 mRNA were increased in the airways of the lungs of BN rats after OA challenge (P < 0.05) and that cells expressing mRNA for IFN-gamma and IL-2 were higher in SD than in BN rats after antigen challenge (P < 0.05) [23].
• Results from PCR showed that prior to antigen challenge, BN rats expressed in their lungs mRNA for IL-4 and -5 and SD rats expressed very little mRNA for IL-5 only [23].
• Both IFN-gamma and IL-4 enhanced MCP-1 mRNA levels but with different kinetics [24].
• B cells from Lewis rats showed a similar IL-4-induced enhancement of RT1.B expression (2.5-fold), whereas, in contrast, RT1.D expression was unmodified [25].
• IL-10 was more effective than IL-4 in suppressing iNOS expression and, interestingly, IL-10 conferred protection against oligodendroglial death evoked by LPS/IFN-gamma [26].

Other interactions of Il4

• In contrast, CD45RC- CD8+ T cells from hepatic allografts pretreated with PVG.r1 blood expressed IL-4, IL-10, and IFN-lambda, but not IL-2 [27].
• Our results showed that the mean values for IL-4 and IL-5 mRNA were increased significantly in sensitized rats compared with control rats [28].
• Both CD4+ and CD8+ T cells are activated in response to allergen challenge in the sensitized rat and express Thelper2 cytokines (IL-4, IL-5 and IL-13) [29].
• In contrast, the brain of S. pneumoniae-inoculated rats showed lower levels of IL-1beta, IL-6 and TNF-alpha, but higher levels of TNF-beta and detectable mRNA expression of IL-4 when compared with Hib-inoculated rats [30].
• The serum level of IL-1 beta and IL-4 showed no significant change [31].

Analytical, diagnostic and therapeutic context of Il4

• Inhibition of angiogenesis by interleukin-4 gene therapy in rat adjuvant-induced arthritis [2].
• High performance liquid chromatography (HPLC)-purified 2B11-BCGF (MW approximately 20,000 daltons) stimulates the proliferation of astrocytes in a dose-dependent fashion [19].
• The aim of this study was to analyze effects of mechanical force during orthodontic tooth movement, in the pressure zone, on the induction of interferon-gamma (IFN-gamma) as a proinflammatory cytokine of Th1 type and interleukin-4 (IL-4)/IL-10 as anti-inflammatory cytokines of Th2 type [32].
• Interleukin-10, interleukin-4, and transforming growth factor-beta differentially regulate lipopolysaccharide-induced production of pro-inflammatory cytokines and nitric oxide in co-cultures of rat astroglial and microglial cells [33].
• No IL-10 was seen in isografts, but IL-4 was detected in 3/5 isografts [34].

References