[The therapeutic effect of soluble inducible costimulator fusion protein on inflammation in a murine model of allergic asthma].
OBJECTIVE
To examine the therapeutic effect of inducible costimulator fusion protein (ICOS-Ig) on airway inflammation in a murine model of allergic asthma.


METHODS
Thirty-two healthy female BALB/c mice were randomly divided into four groups, namely the asthma group (group A), the ICOS-Ig treated group (group B), the control antibody group (group C), and the saline challenged group (group D), with 8 mice in each group. ICOS-Ig was produced by the eukaryotic expression technology. A murine model of allergic asthma was made by sensitizing animals with ovalbumin and exposing them to repeated ovalbumin inhalation challenges. After the mice were treated with ICOS-Ig at the time of ovalbumin challenge, the airway responsiveness, inflammatory cells and the cytokine content in bronchoalveolar lavage fluid (BALF), the level of IgE and Th1/Th2 in blood, and the lung histology were measured to observe the effect of the treatment on asthma in vivo.


RESULTS
(1) FACS analysis confirmed that ICOS-Ig had the binding activity to B220 murine splenocytes. (2) Trans-pulmonary pressure change was significantly reduced in mice from group B [(33 +/- 12)%] compared with group A [(58 +/- 10)%, P < 0.01]. The total cell numbers of BALF in mice from group B [(5.9 +/- 3.1) x 10(7)/L] were decreased compared with group A [(22.6 +/- 5.3) x 10(7)/L, P < 0.01]. The percentage of eosinophils in BALF in mice from group B (0.020 +/- 0.020) was reduced significantly as compared with group A (0.070 +/- 0.030, P < 0.01). IL-4 content in BALF was reduced in mice from group B [(77 +/- 31)ng/L] compared with group A [(179 +/- 44) ng/L, P < 0.01]. IgE in blood was decreased in mice from group B [(175 +/- 33)microg/L] compared with group A [(282 +/- 22)microg/L, P < 0.01]. Th2 cell numbers in blood were reduced in mice from group B [(4.5 +/- 1.0)% ] compared with group A [(11.1 +/- 2.5)%, P < 0.01]. (3) Compared with group A, the pulmonary inflammation in group B was relieved and inflammatory changes in airway epithelium were absent.


CONCLUSIONS
ICOS-Ig has an inhibitory effect on inflammation in a murine model of allergic asthma through the blockade of ICOS costimulatory pathway and decreases the level of IgE by altering differentiation of Th1/Th2 lymphocyte subsets in vivo.
Wang
Jian
J
Central Laboratory, Changhai Hospital, Shanghai 200433, China.
Zhang
Jun
J
Long
Xian-lian
XL
Cai
Gang
G
Shen
Qian
Q
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000627:therapeutic use*; D001249:Asthma / Q000209:etiology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E