Inflammatory events in the blood and airways of guinea pigs immunized to toluene diisocyanate.

Abstract

Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational lung disease. We used a model to investigate the course of bronchopulmonary inflammation following immunization with TDI. Guinea pigs were immunized by weekly intradermal injections and challenged with TDI 7 d after the third injection. The animals were killed at different times after challenge and prepared for histologic examination of central and peripheral airways, for immunohistochemical studies of T lymphocyte and eosinophil distribution, and for hematologic and serologic investigations. Specific IgG1 against TDI were present only in immunized animals. In immunized TDI-challenged animals there was a significant increase in the number of metachromatic cells (at 24 h) and a late increase of eosinophils (at 48 h) in the peripheral blood. Mast cells and eosinophils were also increased in the submucosa of central airways of immunized TDI-challenged animals. A similar pattern was observed in the animals' peripheral airways. Additionally, a significant increase of T-lymphocytes and eosinophils was found in the lamina propria at 6 h after exposure in immunized TDI-challenged animals as compared with control animals. In these immunized animals, TDI challenge caused a significant increase of eosinophils, T-lymphocytes, and CD4+ T cells. These findings indicate that intradermal injections of TDI induced a specific antibody response as well as an inflammatory process in both central and peripheral airways. T cells, particularly CD4+ T cells and eosinophils, are the key cells in the immunopathologic alterations induced by TDI in the guinea pig lung.

Histamine Release and Inflammatory Cell Infiltration in Airway Mucosa in Methylene Diphenyl Diisocyanate (MDI)-Induced Occupational Asthma

“…Mast cells [19], activated T cells, and levels of neutrophilic infiltration [20] are also increased in TDI-OA as compared with AEC and AA. These results have been replicated in animal models of TDI-OA [21,22]. Although Bentley et al [23] reported that activated T cells and eosinophils were Fig.…”

Toluylendiisocyanate [MAK Value Documentation in German language, 1999]

“…Hierzu liegen zahlreiche -auch mechanistische -Untersuchungen an Kaninchen und Meerschweinchen sowie in vitro vor, auf die hier nicht näher eingegangen wird. Auf eine Übersichtsarbeit (Raulf-Heimsoth und Baur 1998) und einige neuere Untersuchungen hierzu (Gagniere et al 1996(Gagniere et al , 1997Lastbom et al 1996;Mapp et al 1996;Marek et al 1996) sei verwiesen.…”

Modification of serum proteins in guinea pigs immunized and challenged with toluene diisocyanate

“…They received 3 weekly intradermal injections of 50 yl of 100% TDI (2,4 and 2,6 isomers, ratio 80: 20) or saline into each of 2 dorsal sites (16). The injection of 100 yl of TDI was selected because this dose was able to induce both antibody production (17) and pulmonary sensitization in guinea pigs (16). Seven days after the 3rd injection of TDI, 5 animals of the group of immunized (N=10) and 5 of the group of nonimmunized animals (N=10) were challenged with TDI in a glass chamber (30 1).…”

“…Seven days after the 3rd injection of TDI, 5 animals of the group of immunized (N=10) and 5 of the group of nonimmunized animals (N=10) were challenged with TDI in a glass chamber (30 1). The challenge was done as previously described (16). All the immunized guinea pigs showed local irritation at the sites of the 2nd and 3rd injection of TDI.…”

“…Previously, we developed an animal model of TDIinduced asthma in guinea pigs, and we found an inflammatory cellular response in both the central and peripheral airways of immunized animals challenged by TDI, r i t h an increase of T-lymphocytes, mast cells, and eosinophils in the submucosa of the central airways (16). We also found an inflammatory response in peripheral blood that was characterized by an increase in metachromatic cells 24 hours after the TDI-challenge and a late increase in eosinophils 48 hours after the challenge.…”