SB-273005, an antagonist of αvβ3 integrin, reduces the production of Th2 cells and cytokine IL-10 in pregnant mice

Abstract

Pregnancy is associated with complex immunereactions. In the present study, the effect of SB-273005, an antagonist of αvβ3 integrin, on the alterations of T helper (Th) cells and their derived cytokines that occur during pregnancy was investigated in mice. Five non-pregnant mice were used as a negative control. Mice were impregnated by co-housing females and males at a ratio of 2:1 overnight and pregnancy was confirmed by the appearance of vaginal plugs the following morning. Day 1 (D1) pregnant mice were randomly divided into two groups (n=20) and were administered either dimethylsulfoxide (mock treatment) or SB-273005 (3 mg/kg) by gavage at D3, D4 and D5. At D8, the levels of Th1 and Th2 cells and interleukin (IL)-2 and IL-10 in the spleen and peripheral blood were determined using flow cytometry and enzyme-linked immunosorbent assay. Pregnancy significantly increased the ratio of Th2:Th1 cells in the spleen compared with that in non-pregnant mice (P<0.01). However, this increase was significantly reduced by SB-273005 (P<0.001). Furthermore, whilst pregnancy decreased Th1 cell-produced IL-2 levels and increased Th2 cell-derived IL-10 levels, SB-273005 reversed both processes (P<0.05 for IL-2; P<0.01 for IL-10). The results from the present study demonstrated that pregnancy induces changes in the spleen, including a reduction of IL-2 and an increase in IL-10 production by Th1 and Th2 cells, respectively, as well as an upregulation of the Th2:Th1 ratio in the spleen. These immunological changes are reversed by SB-273005, indicating an important role for αvβ3 integrin in mediating these immunological alterations.