The effects of intravenous immunglobulin on lipopolysaccharide induced fetal brain inflammation

Intrauterine infection / inflammation is one of the known important reasons for preterm birth. Fetal exposure to infection / inflammation results from prolonged neuroinflammatory response in fetal brain damage. Fetal inflammatory response syndrome (FIRS) which actually develops as a protective mechanism, causes organ damage when proinflammatory cytokines are released. It is known that intravenous immunoglobulin (IVIG) acts over cytokines and prevents inflammatory processes. In this study our purpose was to investigate the effects of IVIG on lipopolysaccaride (LPS) induced brain inflammation in neonates by determining cytokine levels and caspase activity. 180 infant rats were included and they were divided into 6 groups of 30 rats each. The mothers of Group 1 and 4 rats were administered SF, intraperitoneally at 0 hour, equal to the LPS volume , on the 19th day of their gestation. Mothers of Groups 2, 3, 5, 6 were given LPS intraperitoneally at 0 hour on the 19th day of their gestation. Two hours after LPS or SF administration, intravenous SF was given to Group 1, 3, 4, 6 mothers and IVIG to Group 2 and 5 mothers. Hysterectomy was performed in Group 1, 2, 3 mothers at 4th hour and Group 4, 5, 6 mothers at 24th hour and the babies were given birth and the brains were extracted. In 4th hour Groups, TNF-α levels of Group 2 (4th hour LPS+IVIG) were significantly lower than the levels of Group 1 (4th hour SF+SF) (p=0.023) and Group 3 (4th hour LPS+SF) (p:0.002). The levels of Group 1 (4th hour SF+SF) were also significantly lower than the levels of Group 3 (4th hour LPS+SF) (p:0.003) [Group 2 (LPS+IVIG) < Group 1 (SF+SF) < Group 3 (LPS+SF)] . Similarly, in 4th hour Groups, IL-1β levels of Group 2 (4th hour LPS+IVIG) were significantly lower than the levels of Group 1 (4th hour SF+SF) (p<0.001) and Group 3 (4th hour LPS+SF) (p<0.001). The levels of Group 1 (4th hour LPS+IVIG) were also significantly lower than the levels of Group 3 (4th hour LPS+SF) (p<0.001) [Group 2 (LPS+IVIG) < Group 1 (SF+SF) < Group 3 (LPS+SF)]. In 24th hour Groups; no conclusion could be obtained with TNF-α levels. The difference between IL-1β levels of Group 4 (24th hour SF+SF) and Group 5 (24th hour LPS+IVIG) were insignificant but, both of them were significantly lower than the levels of Group 6 (24th hour LPS+SF) (p=0.041 for Groups 4 and 6; p<0.001 for Groups 5 and 6) [(Group 5 (24th hour LPS+IVIG) ≠ Group 4 (24th hour SF+SF ) < Group 6 (24th hour LPS+SF)]. No significant difference was detected between caspase 3 activity levels of Group 4 (24th hour SF+SF) and Group 5 (24th hour LPS+IVIG) (p=0.47). However caspase 3 activity level of Group 6 (24th hour LPS+SF) was significantly higher than the activity levels of Group 4 (24th hour SF+SF) (p=0.031) and Group 5 (24th hour LPS+IVIG) (p=0.013) [Group 4 (24th hour SF+SF) ≠ Group 5 (24th hour LPS+IVIG) < Group 6 (24th hour LPS+SF)]. Our results suggest that, IVIG; may be effective in the prevention of central nervous system damage, induced by inflammation, by decreasing IL-1β levels and caspase 3 activity in brain tissue.