IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice

Abstract

We investigated the effects of interleukin (IL)-10 administration on allergen-induced Th2 cytokine production, eosinophilic inflammation, and airway reactivity. Mice were sensitized by intraperitoneal injection of ragweed (RW) adsorbed to Alum and challenged by intratracheal instillation of the allergen. Sensitization and challenge with RW increased concentrations of IL-10 in bronchoalveolar lavage (BAL) fluid from undetectable levels to 60 pg/ml over 72 h. Intratracheal instillation of 25 ng of recombinant murine IL-10 at the time of RW challenge further elevated BAL fluid IL-10 concentration to 440 pg/ml but decreased BAL fluid IL-4, IL-5, and interferon-gamma levels by 40-85% and eosinophil numbers by 70% (P < 0.0001). Unexpectedly, the same IL-10 treatment increased airway reactivity to methacholine in spontaneously breathing mice that had been sensitized and challenged with RW (P < 0.001). IL-10 treatment in naive animals or RW-sensitized mice challenged with PBS failed to increase airway reactivity, demonstrating that IL-10 induces an increase in airway reactivity only when it is administered in conjunction with allergic sensitization and challenge. The results demonstrate that IL-10 reduces Th2 cytokine levels and eosinophilic inflammation but augments airway hyperreactivity. Thus, despite its potent anti-inflammatory activity, IL-10 could contribute to the decline in pulmonary function observed in asthma.

Repetitive measurements of pulmonary mechanics to inhaled cholinergic challenge in spontaneously breathing mice

“…Importantly, the results of serial cholinergic challenges were stable and similar among nonsensitized animals. Despite there being small intrastrain variability in AR to MCh challenge consistent with other reports (24,28), no evidence of tolerance or potentiation of cholinergic RL and Cdyn responsiveness was present with repeated measurements for as long Values are means Ϯ SE; n ϭ 8 mice/group. Leucocytes were recovered from BAL fluid according to Table 1.…”

“…To measure transpulmonary pressure (Ptp), a water-filled PE-90 tubing was inserted into the esophagus to the level of the midthorax and coupled to a pressure transducer (model P75, HSE-Harvard) (24). The optimal positioning of the esophageal tube was in the lower one-third of the esophagus where we monitored maximum negative pressures.…”

“…Histopathological evaluation of the larynx and trachea was performed by a pathologist blinded to treatment of the groups. Epithelial erosions and inflammation were scored using a subjective semiquantitative scale of 0 (none), 1 (minimal), 2 (mild), 3 (moderate), and 4 (severe) as previously described (24).…”

Interleukin-10 Induces Uteroglobin-related Protein (UGRP) 1 Gene Expression in Lung Epithelial Cells through Homeodomain Transcription Factor T/EBP/NKX2.1

“…We previously hypothesized that UGRP1 may be involved in regulating lung inflammation (1,14). In support of our hypothesis, intranasally administered IL-10 reduced production of Th-2 cytokines such as IL-4 and IL-5, and eosinophilia in bronchoalveolar lavage fluid of ragweed-induced allergic mice (45). Similarly, IL-10 abrogated ovalbumininduced airway inflammation and tumor necrosis factor-␣ production (46).…”

Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes

“…IL10 reduces IL4 and IL5 expression as well as IgE titers and eosinophil rates [Moore et al, 1993;van Scott et al, 2000]. Its expression is significantly reduced in asthmatics [Borish et al, 1996], which may be partly due to the IL10-592A SNP in the promoter re-gion [Rosenwasser and Borish, 1997].…”