Mycobacterium bovis BCG killed by extended freeze-drying reduces airway hyperresponsiveness in 2 animal models.
BACKGROUND
Live BCG administered intranasally to mice inhibits the development of ovalbumin (OVA)-induced eosinophilia and airway hyperresponsiveness (AHR). It is unacceptable to treat human subjects intranasally with live BCG.


OBJECTIVE
We investigated whether BCG killed by extended freeze-drying (EFD) and subcutaneously injected has a protective effect in murine and guinea pig models of allergic airway inflammation.


METHODS
Mice were OVA sensitized (days 0 and 7), treated subcutaneously (day 14) with EFD and live or heat-killed BCG, and then OVA challenged (day 42). OVA-sensitized mice (days 0 and 7) were challenged (day 14) and EFD treated (day 18) before OVA rechallenge (day 46) to demonstrate the capacity of EFD to reverse the established lung inflammation. Guinea pigs were OVA sensitized (days 0 and 14), treated intradermally (day 35) with EFD, and OVA challenged (days 90-105).


RESULTS
In mice and guinea pigs EFD treatment reduced AHR. Among 3 BCG preparations, only EFD efficiently reduced AHR, eosinophilia, and the recruitment of dendritic cells to the lungs after OVA challenge. The protective effect of EFD is associated with production of the immunoregulatory cytokine IL-10. Moreover, EFD treatment did not induce toxic effects or delayed-type hypersensitivity to mycobacterial antigens; that is, it did not interfere with the diagnosis of tuberculosis.


CONCLUSIONS
EFD administered subcutaneously inhibits the development of allergic airway inflammation and prevents AHR without inducing delayed-type hypersensitivity and side effects associated with live or heat-killed BCG.
Laboratoire d'Immunothérapie, Institut Pasteur Paris, Paris, France.
Micheline
M
Lagranderie
Mohammad
M
Abolhassani
Jeroen
J
Vanoirbeek
Jean
J
Lefort
Marie-Anne
MA
Nahori
Jose-Roberto
JR
Lapa E Silva
Michel
M
Huerre
Boris
B
Vargaftig
Gilles
G
Marchal
D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001991:Bronchitis / Q000209:etiology / Q000473:pathology; D003713:Dendritic Cells / Q000473:pathology; D004802:Eosinophilia / Q000209:etiology / Q000473:pathology; D005612:Freeze Drying; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000150:complications; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000209:etiology / Q000473:pathology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D001500:BCG Vaccine; D015164:Vaccines, Inactivated; D016753:Interleukin-10; D010047:Ovalbumin