Effect of Th2 cytokine antagonist treatments on chemical-induced allergic response in mice

Abstract

To understand better the cellular and molecular mechanisms of chemical-induced occupational asthma, we examined the effects of the Th2 cytokine antagonists interferon-gamma (IFN-gamma), interleukin (IL)-12 and anti-IL-4 on the balance of the Th1/Th2 response induced by trimellitic anhydride (TMA) and phthalic anhydride (PA). Eight- to ten-week-old BALB/c mice were assigned to be exposed to either TMA or PA plus one of these Th2 cytokine antagonists. Both TMA (25% and 12.5% for sensitization and challenge, respectively) and PA (12.5% and 6.25% for sensitization and challenge, respectively) induced a Th2 response marked by an increasing production of IL-4 and IL-10 in the supernatants of ex vivo spleen cells cultured with concanavalin A and also of serum total IgE. Co-administration of IL-12 and antiIL-4 deviated these PA- or TMA-induced Th2 responses, as judged by an increasing serum total IgG2a production (up to 14-fold), associated with a slight decrease of IL-4 in three out of four experiments and of IL-10 in all four experiments. Co-administration of IFN-gamma, however, had only one weak effect. These findings suggest that the chemical-induced Th2-biased response may be diverted during an induction period by exogenous administration of the Th2 cytokine antagonists, particularly IL-12 and the anti-IL-4 antibody. These results would significantly enhance our understanding of the Th1/Th2 response induced by chemicals.

Cells and mediators in diisocyanate-induced occupational asthma

“…Airway inflammation, goblet cell hyperplasia, epithelial cell alterations, airway hyperresponsiveness, Th2 cytokine expression, and elevated TDI-specific serum IgE and IgG antibodies were observed [54]. In particular, CD4 þ T cells and the expression of Th2 cytokines, including IL-4 and IL-13, were predominantly elevated [55], and Th2 cytokine antagonists (IL-12 or anti-IL-4 antibody) could divert diisocyanate-induced Th2-biased responses [56]. However, CD8 þ T cells and Th1 cytokine involvement was also found in diisocyanate-induced occupational asthma [56].…”

“…In particular, CD4 þ T cells and the expression of Th2 cytokines, including IL-4 and IL-13, were predominantly elevated [55], and Th2 cytokine antagonists (IL-12 or anti-IL-4 antibody) could divert diisocyanate-induced Th2-biased responses [56]. However, CD8 þ T cells and Th1 cytokine involvement was also found in diisocyanate-induced occupational asthma [56]. IFN-g producing CD8 þ T cells were detected in T-cell clones isolated from bronchial mucosa [57], and neutrophils were found in TDI-induced asthma [28].…”

Investigation of the chemical-induced selective type II (TH2) allergic response in mice: Effect of the length of the sensitizing phase

“…Environmental and lifestyle factors and increasing use of chemicals have often been suggested as contributors to allergies (Peden, 2000;Ban and Hettich, 2005). Multiple chemical sensitivities (MCS) are a representative chemicallyinduced allergy that has emerged as a public health problem worldwide (Howarth, 1998;Kimber and Dearman, 2002;Ban and Hettich, 2005).…”

Acute chlorine gas exposure produces transient inflammation and a progressive alteration in surfactant composition with accompanying mechanical dysfunction

“…Recent data demonstrates that higher Cl 2 doses impair response to subsequent Aspergillus challenge, resulting in increased cell infiltration, but diminished production of several mediators of antimicrobial immunity: superoxide, IL-17 and IL-22 (Gessner et al , 2013). A potential link between the inflammatory response seen in this exposure model and the pathophysiology of repeated exposure to chlorinated compounds may exist, as airway remodeling and hyperresponsiveness to methacholine are thought to result from repeated stimulation by M2/Th2 type cytokines (Ban and Hettich, 2005). Relm-α has an established role in airway and pulmonary vascular remodeling observed in asthma (Dong et al , 2008) and pulmonary hypertension (Angelini et al , 2009) through effects on recruitment of bone-marrow derived cells (Angelini et al , 2010) and promotion of myofibroblast differentiation (Liu et al , 2004).…”