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.

Autism and Immunity: Revisited Study

“…For example, the question of a connection between vaccination and autism is surrounded by controversy. In addition, several studies showing elevated brain-specific antibodies in autism support an autoimmune mechanism (22)(23)(24)(25). However, recently it has been reported that vaccines, as well as autoimmunity do not seem to be the cause of autism.…”

Hypertonic Saline Solution in Children with Adenoidal Hyperytrophy: Preliminary Evidence

“…It was recently reported that treatment with corticosteroids can decrease the size of AH, both using beclomethasone (8) and fluticasone (9)(10)(11)(12)(13). It has also been demonstrated that nasal beclomethasone is capable of decreasing the frequency of adenotonsillectomy (14)(15)(16)(17).…”

Autoimmunity and Parasites

“…Type 1 helper T(Thl) cells produce mainly IFN-y, TNF-~and IL-2, whereas type 2 helper T (Th2) cells produce mainly IL-4, IL-5 and IL-13. Since sclerosis and type 1 diabetes are mainly mediated by Thl cells and allergic diseases by Th2 cells, alteration of the cytokine balance is an appealing threrapeutic possibility (11)(12). There is evidence that the shift in balance between Thl-type cytokines and Th2-type cytokines that occurs during pregnancy alleviates the symptoms of rheumatoid arthritis.…”

“…Up-regulation of either T helper (TH\ or TH 2 cells is pathogenic, and these subsets down-regulate each other. The expression of chemokines/cytokines by trafficking inflammatory T cells is also crucial to autoimmunity.The absence ofthose down-regulating parasites leads to insufficient stimulation of the TH] arm of the immune system and to an overactive TH 2 which in tum leads to asthma, hay fever, multiple sclerosis, etc (11)(12)(13)(14).…”