title: Questioning the Th1/Th2 paradigm in reproduction: peripheral levels of IL-12 are down-regulated in miscarriage patients.
abstract: OBJECTIVE
  It has been postulated that a T helper (Th)1 response is associated with pregnancy failure, whereas a Th2 response contributes to pregnancy maintenance. However, this Thl/Th2 dichotomy has recently been hypothesized to be an oversimplification. To prove this novel hypothesis, we investigated the levels of the Th1-inducer cytokine interleukin (IL)-12 in immunocompetent cells of patients with normal pregnancies (NP) and spontaneous abortion (SA).
  
  
  METHODS
  Presence of intracellular IL-12 was evaluated in CD8+ and CD56-blood and decidual lymphocytes as well as in monocytes and granulocytes by flow cytometry from NP and SA individuals. IL-12 serum levels were measured by enzyme-linked immunosorbent assay (ELISA). We further investigated the effect of recombinant human (rh) IL-12 on the production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha in peripheral leukocytes ex vivo.
  
  
  RESULTS
  In patients suffering from SA we observed lower percentages of IL-12 in lymphocytes, monocytes and granulocytes derived from peripheral blood and decidua, compared with women with normally progressing pregnancies. No differences could be observed when evaluating the levels of IL-12 in the granulocyte population. The IL-12 serum levels were below the ELISA sensitivity limit. Ex vivo stimulation of the peripheral blood cells with increasing doses of IL-12 resulted in a significant decrease of IFN-gamma+, whereas levels of TNF-alpha+ in lymphocytes were unaffected.
  
  
  CONCLUSIONS
  The classical Th1/Th2 paradigm appears to be insufficient to exclusively explain the causes of pregnancy loss. Our current results render us to requestion the role of Th1 cytokines during pregnancy and suggest some protective function of the Th1-inducer cytokine IL-12.
authors.affiliation: Charité, Campus Virchow, Humboldt University, Berlin, Germany.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Zenclussen
authors.forename: Stefan
authors.initials: S
authors.lastname: Fest
authors.forename: Petra
authors.initials: P
authors.lastname: Busse
authors.forename: Ricarda
authors.initials: R
authors.lastname: Joachim
authors.forename: Burghard F
authors.initials: BF
authors.lastname: Klapp
authors.forename: Petra C
authors.initials: PC
authors.lastname: Arck
mesh_terms: D000022:Abortion, Spontaneous / Q000378:metabolism*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D003656:Decidua / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma