title: Antenatal administration of Rh-immune globulin causes significant increases in the immunomodulatory cytokines transforming growth factor-beta and prostaglandin E2.
abstract: 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).
  
  
  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-1alpha; granulocyte-macrophage-colony-stimulating factor; tumor necrosis factor-beta; and interferon-gamma 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-beta1 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-beta2. In addition to TGF-beta, 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-beta1 and PGE2 after RhIG were significant.
  
  
  CONCLUSIONS
  These results indicate that RhIG prophylaxis can induce higher than baseline levels of two strongly immunomodulatory cytokines, TGF-beta 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.
authors.affiliation: Transfusion Immunology Hub, Research & Development, Canadian Blood Services, Toronto, Ontario, Canada. don.branch@utoronto.ca
authors.forename: Donald R
authors.initials: DR
authors.lastname: Branch
authors.forename: Fariba
authors.initials: F
authors.lastname: Shabani
authors.forename: Nicole
authors.initials: N
authors.lastname: Lund
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Denomme
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D015232:Dinoprostone / Q000097:blood* / Q000276:immunology; D004899:Erythroblastosis, Fetal / Q000097:blood* / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage* / Q000276:immunology; D011247:Pregnancy; D012204:Rh-Hr Blood-Group System / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000276:immunology
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen; D016212:Transforming Growth Factor beta; D015232:Dinoprostone