Conjugates of ovalbumin and monomethoxypolyethylene glycol abolish late allergic responses and decrease IL-4 and IL-5 mRNA expression in the rat.
The purpose of this study was to test the therapeutic potential of monomethoxypolyethylene glycol (mPEG) conjugated-allergen using a rodent model of allergic asthma. Previously, this conjugate has been shown to possess the dual capacity of inducing long-term ovalbumin (OA)-specific suppression of the antibody response and inactivating rat mast cells that have been sensitized with murine IgE to OA. Ovalbumin sensitized and challenged Brown Norway rats were studied. Fourteen days after sensitization, a test group of six rats received mPEG-OA solution intratracheally and were challenged 30 min later with aerosolized OA. Another group of seven sensitized rats was similarly challenged with OA 30 min after intratracheal administration of normal saline. A group of six sensitized rats received mPEG-OA solution intratracheally but were challenged with normal saline. Another group of seven sensitized rats received mPEG-BSA solution intratracheally and were challenged 30 min later with aerosolized OA. A final group of five unsensitized rats were neither challenged nor medicated intratracheally. Pulmonary resistance was measured before and for 8 h following inhalation challenge. mPEG-OA treatment had an inhibitory effect on the allergic late airway response, but the early response was not significantly altered. Both mPEG-OA and mPEG-BSA reduced the total cells, eosinophils and neutrophils, in bronchoalveolar lavage and decreased the expression of IL-4, IL-5 and IFN-gamma mRNA. In conclusion, mPEG-OA can prevent the development of allergen-induced late airway responses and reduce airway Th2-type cytokine expression whereas mPEG conjugated to an irrelevant antigen (BSA) is anti-inflammatory but does not affect the late response.
Lavoie
J-P
JP
Department de Sciences Cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, 3200 Sicotte CP5000, St-Hyacinthe, Que., Canada J2S 7C6. jean-pierre.lavoie@umontreal.ca
Maghni
K
K
Taha
R
R
Yang
X-X
XX
Lang
G M
GM
Sehon
A H
AH
Hamid
Q A
QA
Martin
J G
JG
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects; D006632:Histamine / Q000032:analysis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011914:Rats, Inbred BN
D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; D011092:Polyethylene Glycols; D006632:Histamine; D007371:Interferon-gamma; C028210:monomethoxypolyethylene glycol; D010047:Ovalbumin