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Method for treating inflammatory inflammatory diseases using heat shock proteins

A heat shock protein and disease technology, applied in allergic diseases, skin diseases, sensory diseases, etc., can solve problems such as side effects and inability to fight inflammatory reactions

Inactive Publication Date: 2001-11-28
NAT JEWISH MEDICAL & RES CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The use of anti-inflammatory and symptom relievers is a serious problem because of their side effects or their inability to combat the underlying cause of the inflammatory response

Method used

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  • Method for treating inflammatory inflammatory diseases using heat shock proteins
  • Method for treating inflammatory inflammatory diseases using heat shock proteins
  • Method for treating inflammatory inflammatory diseases using heat shock proteins

Examples

Experimental program
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Effect test

Embodiment 1

[0100] The following examples demonstrate that mycobacterial heat shock protein 65 (HSP-65) upregulates T cell proliferative responses following short-term sensitization with ovalbumin in the presence of alum in a mouse model of airway hyperresponsiveness.

[0101] Animal models of disease are invaluable for providing evidence to support a hypothesis or justify human experiments. Mice have many proteins that are greater than 90% homologous to the corresponding human proteins. For the following experiments, the inventors used an antigen-driven mouse system characterized by immune (IgE) responses, reliance on Th2-type responses, and eosinophil responses. This model is characterized by marked airway hyperresponsiveness and its progression.

[0102] Development of a universal mouse system for chronic aerobic antigen exposure (associated with profound eosinophilia and marked, persistent, and progressive airway hyperresponsiveness) provides an unprecedented opportunity to investiga...

Embodiment 2

[0111] The following examples demonstrate that mycobacterial HSP-65 upregulates T cell proliferative responses in an allergic sensitized mouse model following suboptimal sensitization with ovalbumin via aerosol challenge.

[0112] Since immunization with mycobacterial HSP-65 after i.p. sensitization of mice enhanced T cell responses to OA (Example 1), the question arises that antigen-specific T cell responses are often not detected in Under conditions (ie, suboptimal sensitization with ovalbumin), will mycobacterial HSP-65 upregulate the response. In addition, the following experiments were designed to examine how short-term treatment with mycobacterial HSP-65 would affect airway responses (bronchoalveolar lavage (BAL) cellularity and airway response to methacholine stimulation).

[0113] Mice were exposed to OA aerosol (1%) on days 1, 2, 3 and 6 (suboptimal protocol) and received 100 μg of mycobacterial HSP-65 or PBS intravenously on days 1 and 6. It should be noted that in ...

Embodiment 3

[0121] The following examples demonstrate that mycobacterial HSP-65 upregulates T cell proliferative responses in an airway hyperresponsive mouse model optimally sensitized and stimulated with ovalbumin in the presence of alum.

[0122] In the mouse model of airway hyperresponsiveness and allergic sensitization used here, it has been determined that systemic sensitization and local airway stimulation lead to airway responsiveness associated with eosinophilic inflammation of the airways Hypertension (AHR), which is a cardinal feature of asthma (see, for example, Bentley et al., 1992, Am. Res. Res. Res. 146:500-506; 213; or Dunhill et al., 1960, J. Clin. Pathol. 13:27-33; these publications are incorporated herein by reference in their entirety). To investigate the effect of mycobacterial HSP-65 treatment on these pathological changes in the airways, mice were administered intraperitoneally with 20 μg of OA in 100 μl of PBS (Phosphate Buffered Saline) (Grade V , Sigma Chemical ...

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Abstract

This invention relates to a method to protect a mammal from a disease associated with an inflammatory response, and in particular, from an inflammatory disease characterized by eosinophilia, airway hyperresponsiveness and / or a Th2-type immune response. The method includes administration of a heat shock protein to a mammal having such a disease. Formulations useful in the present method are also disclosed.

Description

field of invention [0001] The present invention relates to methods of protecting mammals from inflammatory diseases, particularly diseases characterized by eosinophilia associated with an inflammatory response. Background of the invention [0002] Diseases involving inflammation are characterized by an influx of certain cell types and mediators, the presence of which can lead to tissue damage and sometimes death. Diseases involving inflammation are particularly harmful when they affect the respiratory system, resulting in obstructed breathing, hypoxemia, hypercalcaemia, and lung tissue damage. Obstructive disease of the airways characterized by airflow limitation (ie, airflow obstruction or narrowing) due to airway smooth muscle constriction, edema, and mucus hypersecretion leading to increased respiration, dyspnea, hypoxemia, and hypercalcemia caused by. Although the mechanical properties of the lung during obstructive breathing are common to different types of obstructiv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/08A61K9/12A61K9/14A61K9/48A61K9/70A61K38/00A61K38/16A61K38/17A61K39/395A61K45/00A61K45/06A61K45/08A61K47/10A61K47/44A61K47/46A61K48/00A61P11/00A61P11/06A61P17/00A61P17/04A61P27/14A61P37/00A61P37/08
CPCA61K45/06A61K38/164A61K48/00A61K38/1709A61P11/00A61P11/06A61P17/00A61P17/04A61P27/14A61P33/00A61P37/00A61P37/08A61K38/00
Inventor E·W·盖尔芬德A·F·哈茨库K·V·卢卡克斯
Owner NAT JEWISH MEDICAL & RES CENT
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