IL-13 Neutralization Modulates Function of Type II Polarized Macrophages in vivo in a Murine T-Cell Lymphoma

Abstract

IL-13 is a Th2 cytokine that suppresses the effector function and alters the phenotype and function of macrophages switching to alternatively activated or type II polarized macrophages. The type II polarized macrophages or M2 phenotype differ from normal macrophages greatly in terms of receptor expression, cytokine and NO production, that show tumor promoting function rather than tumoricidal function of classically activated macrophages. The chemokines CCL-22 and CCL-17 produced by either tumor cells or alternatively activated macrophages attract Th2 cells preferentially, which increase the local concentration of Th2 cytokines including IL-13 that further skewed the normal phenotype of macrophages at the site of the tumor micro-environment. Therefore, it is possible to restore the phenotype and function of alternatively activated macrophages by eliminating or blocking the activities of these cytokines. In the present investigation, we show that by blocking the activity/signaling of one of its major constituents IL-13, the iNOS expression and correspondingly NO production increases. The observation signifies its efficacy towards a novel approach for cancer therapy by modulating the function of tumor-associated macrophages (TAM) in vivo for the first time.