Anti-IL13 monoclonal antibody, clone KFT20-6B3 [PE]

Inflammation is a key feature of preterm and term labor. Proinflammatory mediators are produced by gestation-associated tissues in response to pathogen-associated molecular patterns and damage-associated molecular patterns. Interleukin (IL)4, IL10, and IL13 are anti-inflammatory cytokines with potential as anti-inflammatory therapies to prevent preterm birth. The objective of this study was to determine if IL4 and IL13 exert anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated production of proinflammatory cytokines produced by human term gestation-associated tissues (placenta, choriodecidua, and amnion). Both IL4 and IL13 reduced LPS-stimulated IL1B and macrophage inflammatory protein1A; this effect diminished with delay to exposure to either cytokine. There was no effect on LPS-stimulated prostaglandin production. Interleukin 4 receptor alpha (IL4RA) was expressed throughout the placenta, choriodecidua, and amnion, and the inhibitory effects of IL4 and IL13 were IL4RA dependent. Combined IL4 and IL13 did not enhance the anti-inflammatory potential of either cytokine; however, a combination of IL4 and IL10 had a greater anti-inflammatory effect than either cytokine alone. These findings demonstrate that human term gestation-associated tissues are responsive to the anti-inflammatory cytokines IL4 and IL13, which could downregulate LPS-induced cytokine production in these tissues. Antiinflammatory cytokines might offer an adjunct to existing therapeutics to prevent adverse obstetric outcome.

Background: Although previous studies had reported an important role of interleukin 13 (IL13) and its genetic polymorphisms in atopic dermatitis (AD), many of these previous reports focused on the missense variant rs20541 (Gln144Arg) without fine mapping of the gene region. Objective: To analyze the potential associations of other IL13 variants and their haplotypes with AD and assess total serum immunoglobulin E (IgE) levels. Methods: We performed fine mapping of single-nucleotide polymorphisms (SNPs) within the IL13 gene in a pilot study of 495 children with AD and 444 healthy controls. Then, we conducted a replication study of 757 children with AD and 1620 healthy controls to evaluate the association between the rs20541 variant of IL13 and AD. Results: In the pilot study, the rs20541 and rs1295685 SNPs in the 3'-untranslated region of IL13 had significant associations with AD (P < .001 and .01, respectively). In addition, 2 haplotypes (BL2_htl and BL2_ht2), which harbored the significant rs20541 and rs1295685 SNPs, had an association with AD (minimum P= .006). BL2_htl and BL2_ht2 had nominal signals associated with the total serum IgE levels (P < .05) but not with the severity of AD (P > .05). In the replication study, rs20541 was associated with the total serum IgE levels but not with the severity of AD. Conclusion: An additional IL13 gene SNP, rs1295685, has a strong linkage disequilibrium with rs20541, and its haplotypes are associated with AD and the total serum IgE levels. (C) 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.