In vivo treatment with anti‐interleukin‐13 antibodies significantly reduces the humoral immune response against an oral immunogen in mice

Abstract

SUMMARYInterleukin-13 (IL-13) is a cytokine which significantly enhances the proliferation and differentiation of B lymphocytes. We therefore evaluated its role in the formation of a humoral immune response in vivo. Upon oral immunization with the B subunit of Escherichia coli heat-labile enterotoxin (LT-B), rapid upregulation of IL-13 mRNA expression in the mesenteric lymph nodes of LT-B intubated mice occurred. This result suggested that IL-13 might be involved in the formation of a mucosal antibody response against LT-B if this cytokine was in fact secreted. To test this possibility, the coding region for murine IL-13 was cloned into the pFLAG-1 expression vector. Recombinant murine IL-13 was purified from bacterial lysates and used as an immunogen to produce polyclonal anti-IL-13 antibodies. Groups of BALB/c mice treated in vivo with anti-IL-13 antibody 2 days before and on the day of oral immunization with LT-B had significantly reduced intestinal IgA and serum IgG and IgA anti-LT-B antibody responses when compared to mice treated with control antibody. Furthermore, groups of mice primed with LT-B and then treated with anti-IL-13 antibody prior to oral immunization with a second dose of LT-B also had significantly reduced intestinal IgA and serum IgG and IgA anti-LT-B antibody titres compared to controls. In vitro LT-B restimulation experiments using splenic mononuclear leucocytes isolated from LT-B primed mice treated with anti-IL-13 antibody demonstrated decreased expression of IL-4 and IL-13 mRNA and decreased IL-4 secretion when compared to controls. Together these results demonstrate an important role for IL-13 in the formation of a humoral immune response at mucosal surfaces.

IL-33, an Interleukin-1-like Cytokine that Signals via the IL-1 Receptor-Related Protein ST2 and Induces T Helper Type 2-Associated Cytokines

“…The increased eosinophil levels induced by IL-33 could be associated with an increase in IL-5 expression, while IgE and IgA synthesis could be associated with IL-4 and IL-13 expression (Bost et al, 1996;Chomarat and Banchereau, 1998;Roboz and Rafii, 1999). Therefore, we tested whether IL-33 could induce expression of T H 2-associated cytokines in vivo.…”

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

“…[42][43][44] The administration of sIL-4R or antagonistic IL-4 mutant proteins is a novel approach to inhibit allergic inflammation. These proteins directly inhibit IL-4 binding and do not induce host immune responses to these proteins.…”

Impaired Development of Th2 Cells in IL-13-Deficient Mice

“…Thus, IL-13 plays a critical role in the development of a number of Th2 cell-mediated responses in vivo. Interestingly, treatment of mice with a polyclonal antibody raised against mIL-13 resulted in a decrease in the levels of IL-4 being made by antigen-specific T cells in response to immunization (Bost et al, 1996), suggesting that inhibiting IL-13 function results in impaired lineages. Using a combination of in vitro assays and in (B) Southern blot analysis of F2 tail DNA.…”