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

BACKGROUND: 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). STUDY DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.