Abstracts

Mycobacterium leprae HSP 65kD prevents ragweed-induced airway hyperresponsiveness in a murine model of asthma.

Abstract presented at ATS 2001 (American Thoracic Society) - San Francisco, CA May 18-23, 2001 as printed in Am J Respir Crit Care Med 2001; 163(5): A522

Santeliz J.V. (1), Winnett M. (2), Wills-Karp M. (3)

(1) Dept. of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, USA.
(2) Stressgen Biotechnologies, Inc., Collegeville, PA, USA.
(3) Children's Hospital Medical Center, Cincinnati, OH, USA.

Asthma is an immunologically mediated disease of the airways characterized by airway obstruction, airway inflammation and an increase in airway responsiveness. TH2 cytokines play an important role as mediators of this response. Epidemiological studies have shown that exposure to bacterial products promotes a TH1 environment in the lung and ultimately inhibits TH2 responses characteristic of asthma. Heat shock proteins are induced in many cells upon stress conditions and are able to induce gene expression of TH1 cytokines. Thus we hypothesized that administration of HSP may ameliorate the TH2 dominated immune response characteristic of asthma. To test this hypothesis, we sensitized Balb/CJ female mice twice with ragweed (150ug protein). One week later mice were challenged with an aspirated dose of ragweed (200ug protein). At the time of sensitization and first challenge mice were treated subcutaneously with Mycobacterium leprae HSP 65Kd (200ug). Mice were challenged with antigen one week after the last treatment and airway responsiveness to i.v. acetylcholine (APTI) was assessed. Ragweed sensitized mice showed airway hyperresponsiveness, BAL eosinophilia, elevated levels of serum antigen specific IgE and goblet cell metaplasia. HSP 65Kd significantly reversed airway hyperresponsiveness (p=0.009) in ragweed sensitized mice concomitant with a reduction in total number of eosinophils (p=0.02) and lymphocytes (p=0.001) in BAL fluid. HSP 65Kd treatment decreased total serum IgE levels (p=0.007) and antigen specific IgG1 levels (p=0.01) in ragweed sensitized mice. These results suggest that heat shock proteins may provide an effective therapeutic tool for asthma.