Animal models for diisocyanate asthma: answers for lingering questions.

نویسندگان

  • Victor J Johnson
  • Joanna M Matheson
  • Michael I Luster
چکیده

PURPOSE OF REVIEW Diisocyanates are the leading cause of occupational asthma, the most commonly reported lung disease associated with the workplace. Clinical studies have implicated the immune system in the pathogenesis of occupational asthma, but ethical and moral issues prevent mechanistic investigations in humans. For this reason, the development and characterization of animal models are germane to further understanding of diisocyanate occupational asthma and to identify avenues for therapeutic intervention. This review will highlight important features of existing experimental animal models with emphasis on new developments. RECENT FINDINGS Experimental animal models of diisocyanate occupational asthma have demonstrated an immunological basis for the disease. Mice can be sensitized by dermal or respiratory exposure, suggesting that either exposure route may be important in the workplace. Recent findings show that sensitized mice develop airway hyperreactivity and inflammation, reflective of human disease. The transfer of lymphocytes or serum from sensitized mice can cause clinical disease in naive mice. Transgenic animals have identified a role for specific immunity, including the involvement of T-helper type 1/2 responses as well as CD4 and CD8 T cells in diisocyanate occupational asthma. Recent animal models have shown that sensitization can occur through subchronic inhalation of vapor-phase diisocyanate at levels as low as 20 ppb. SUMMARY Recent progress using animal models has been instrumental in furthering current understanding of the involvement of the immune system in disease pathogenesis. The demonstration of diisocyanate occupational asthma in a murine model after sub-chronic inhalation exposure at relevant exposure levels should provide opportunities for more accurate risk assessment data.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Maternal allergic contact dermatitis causes increased asthma risk in offspring

BACKGROUND Offspring of asthmatic mothers have increased risk of developing asthma, based on human epidemiologic data and experimental animal models. The objective of this study was to determine whether maternal allergy at non-pulmonary sites can increase asthma risk in offspring. METHODS BALB/c female mice received 2 topical applications of vehicle, dinitrochlorobenzene, or toluene diisocyan...

متن کامل

The role of thromboxane A2 in the pathogenesis of airway hyperresponsiveness.

Airway hyperresponsiveness to a variety of bronchoconstrictor mediators and physical stimuli, such as exercise, is present in patients with asthma [1]. Inhalation of inflammatory stimuli such as allergens [2] or occupational sensitizing agents [3] in sensitized subjects, the atmospheric pollutant ozone [4], or the development of viral upper respiratory tract infections (5] can cause transient a...

متن کامل

Development of a respiratory sensitization/elicitation protocol of toluene diisocyanate (TDI) in Brown Norway rats to derive an elicitation-based occupational exposure level.

Toluene diisocyanate (TDI), a known human asthmagen, was investigated in skin-sensitized Brown Norway rats for its concentration×time (C×t)-response relationship on elicitation-based endpoints. The major goal of study was to determine the elicitation inhalation threshold dose in sensitized, re-challenged Brown Norway rats, including the associated variables affecting the dosimetry of inhaled TD...

متن کامل

Asthma Symptoms and Specific IgE Levels among Toluene Diisocyanate (TDI) Exposed Workers in Tehran, Iran

BACKGROUND Toluene diisocyanate (TDI) is an imperative chemical substance used in the production of polyurethane foams, elastomers, paints and coatings that cause a variety of health problems in workers who are exposed in work places. This study aimed to determine the asthma symptoms and serum specific IgE levels in TDI exposed workers and comparing the results with healthy control group. MET...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Current opinion in allergy and clinical immunology

دوره 4 2  شماره 

صفحات  -

تاریخ انتشار 2004