Document 0979
 DOCN  M9650979
 TI    Effect of IFN-gamma administration in virgin and pregnant mice:
       distribution of lymphoid and myeloid cells in the spleen.
 DT    9505
 AU    Athanassakis I; Vassiliadis S; Department of Biology, University of
       Crete, Greece.
 SO    Eur Cytokine Netw. 1995 May-Jun;6(3):167-76. Unique Identifier :
       AIDSLINE MED/96159497
 AB    Administration of Interferon-gamma (IFN gamma) is used in the
       therapeutic approach for mainly cancer treatment and viral infections in
       vivo. Recently we observed some important pathologic dysfunctions caused
       by IFN-gamma administration to pregnant mice. This treatment affected
       not only the growth and development of the feto-placental unit, but
       also, among other hematologic disorders, caused splenomegaly to the
       mother. In an effort to explain the observed hypersplenism, we have
       analysed the behaviour of macrophages, B and T lymphocytes in the spleen
       of virgin and pregnant mice after intraperitoneal administration of low
       IFN-gamma doses. Although the percentage of myeloid Mac-1 and F4/80
       positive cells in spleen cell suspensions of virgin and pregnant mice do
       not change with the IFN-gamma treatment, immunoperoxidase staining of
       frozen spleen sections shows that in pregnant mice the monocytic cells
       accumulate at the central white pulp area of the organ, whereas in
       non-pregnant mice these cells are mainly found at the peripheral red
       pulp area. In contrast, the same treatment was shown to increase the
       numbers of Ly5 positive B cells in both virgin and pregnant mice,
       whereas B cells were found to form clusters only in the case of pregnant
       animals. We also show that IFN-gamma increases the numbers of Tcyt/sup
       (Ly2 positive cells) and TH (L3T4 positive cells) in the spleen of
       virgin mice but not in pregnant mice. Both populations display a
       physiologic distribution in the white pulp of the organ as assessed by
       immunoperoxidase staining of frozen spleen sections. Interestingly, the
       distribution pattern of IL-2- and IL-4-producing cells, which reflects
       the presence of Th1 and Th2 subpopulations was different in pregnant and
       virgin mice. Gestating females had IL-2 producing cells dispersed in the
       white pulp area, whereas IL-4 producing cells formed clusters mainly at
       the periphery of the organ. Virgin females had almost undetectable
       levels of IL-4 producing cells, whereas IL-2 producing cells were found
       at the periphery. Our results indicate that IFN-gamma alters the
       equilibrium between Th1 and Th2 cells, which in turn is responsible for
       the redistribution of myeloid and lymphoid cells in the spleen of
       pregnant mice thereby explaining the development of an active
       immune/inflammatory reaction.
 DE    Animal  Antigens, Differentiation, T-Lymphocyte/ANALYSIS
       B-Lymphocytes/DRUG EFFECTS  Biological Response
       Modifiers/*PHARMACOLOGY/TOXICITY  Cell Count/DRUG EFFECTS  Female  Fetal
       Development/DRUG EFFECTS  Hypersplenism/CHEMICALLY INDUCED/PATHOLOGY
       Immunoenzyme Techniques  Interferon-gamma,
       Recombinant/*PHARMACOLOGY/TOXICITY  Interleukin-2/BIOSYNTHESIS
       Interleukin-4/BIOSYNTHESIS  Lymphocyte Subsets/*DRUG EFFECTS  Mice
       Mice, Inbred BALB C  Monocytes/*DRUG EFFECTS  Pregnancy  Pregnancy
       Complications/CHEMICALLY INDUCED/PATHOLOGY  Pregnancy, Animal/*DRUG
       EFFECTS  Spleen/CYTOLOGY/*DRUG EFFECTS  Splenomegaly/CHEMICALLY
       INDUCED/PATHOLOGY  Support, Non-U.S. Gov't  Th1 Cells/DRUG
       EFFECTS/SECRETION  Th2 Cells/DRUG EFFECTS/PHYSIOLOGY/SECRETION  JOURNAL
       ARTICLE

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