Intravenous Immunoglobulin Treatment in Women with Recurrent Abortions: Increased Cytokine Levels and Reduced Th1/ Th2 Lymphocyte Ratio in Peripheral Blood


Address reprint requests to Hideto Yamada MD PhD, Lecturer, Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, Kita-ku N15 W7, Sapporo 060–8638, Japan.


PROBLEM:  The aim of this study was to investigate changes in peripheral blood Th1/Th2 cytokine levels and lymphocyte ratios after massive intravenous immunoglobulin (MIVIg) treatment for women with recurrent spontaneous abortion (RSA) of unexplained etiology.

METHOD OF STUDY:  Serum Th1 (IFN-γ, TNF-α) and Th2 cytokine (IL-4, IL-10) levels were assessed by ELISA methods (n = 9) and peripheral blood Th1/Th2 lymphocyte ratios (n = 4) by flow cytometry before and after MIVIg treatments in women with four or more consecutive RSA.

RESULTS:  Pre-treatment serum IFN-γ (0.06 ± 0.09 pg/mL, mean ± SD), TNF-α (0.21 ± 0.45 pg/mL), IL-4 (0.70 ± 1.16 pg/mL), and IL-10 (1.12 ± 1.67 pg/mL) increased to 0.17 ± 0.16 pg/mL, 0.77 ± 0.28 pg/mL, 1.82 ± 0.89 pg/mL, and 3.44 ± 0.48 pg/mL, respectively, after MIVIg treatments (P < 0.05). CD4-positive IFN-γ/IL-4 lymphocyte ratios (17.3 ± 9.1) were reduced to 11.5 ± 7.1 after treatment (P < 0.05).

CONCLUSIONS:  Massive intravenous immunoglobulin treatments increased peripheral blood cytokine levels and decreased Th1/Th2 lymphocyte ratios; thus, MIVIg treatments modify the peripheral Th1/Th2 balance.