Antenatal administration of Rh-immune globulin causes significant increases in the immunomodulatory cytokines transforming growth factor-β and prostaglandin E2

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Production of specific cytokines in response to administration of Rh-immune globulin (RhIG) was examined to assess the mechanism of inhibition of the anti-D production and prevention of hemolytic disease of the newborn (HDN).


Plasma levels of 17 different cytokines before and 48 hours after antenatal administration of anti-D were measured in 10 women candidates for prophylaxis with RhIG.


No striking changes were observed in levels of the cytokines interleukin (IL)-1 sRII, IL-12 p40, IL-16, or monocyte chemoattractant protein-1. Levels of IL-4, −5, −10, −13, and −17; macrophage inflammatory protein-1α; granulocyte-macrophage–colony-stimulating factor; tumor necrosis factor-β; and interferon-γ remained below detection levels both before and after testing. IL-1ra levels, however, showed a slight to moderate decrease in 7 of 10 women after RhIG administration. In contrast, levels of TGF-β1 increased more than 1.3-fold in 7 of 10 women and more than 2-fold in 4 of 10 women; in 1 instance the increase was more than 5-fold and this woman also had a significant increase in TGF-β2. In addition to TGF-β, 5 of 10 women had a modest increase (>1.5-fold) in prostaglandin E2 (PGE2). Analyses of the combined results of the 10 women showed that increases in both TGF-β1 and PGE2 after RhIG were significant.


These results indicate that RhIG prophylaxis can induce higher than baseline levels of two strongly immunomodulatory cytokines, TGF-β and PGE2. These findings represent one possible mechanism for the inhibition of the primary immune response to the D antigen in women receiving RhIG prophylaxis for prevention of HDN.

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