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i

2′, 3′-Dideoxyinosine Inhibits the Humoral Immune Response in Female B6C3F1 Mice by Targeting the B Lymphocyte

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  • Description:
    2',3'-Dideoxyinosine (ddI) is a purine nucleoside analog currently being used for the treatment of HIV-positive individuals and patients with AIDS. Preliminary immunotoxicity studies have shown that a consequence of ddI treatment in female B6C3F1 mice is the inhibition of the humoral immune response. This effect was dose dependent in a range of 100 to 1000 mg/kg with a no observed adverse effect level of less than 100 mg/kg for a 28-day treatment period. These studies were undertaken to investigate the immune cell target of ddI and to determine the mechanism of this toxicity. B6C3F1 mice were treated with 1000 mg/kg/day by oral gavage for 28 days. The B lymphocyte was identified as the cellular target of ddI through separation-reconstitution experiments of the adherent and nonadherent cell populations and of the T and B lymphocyte populations. These studies revealed a deficit in the ability of the nonadherent cells from ddI-treated mice to mount a normal antibody response to sRBC. A further separation of the nonadherent cells into T and B cells revealed a decreased ability of ddI-treated B cells to develop specific humoral immunity. Additional studies were undertaken to determine the mechanism by which ddI is affecting the B cell. Surface marker analysis of splenocytes revealed no difference in the cell populations between vehicle- and ddI-treated mice. B cell proliferation was also unaffected as shown by incubation with either a polyclonal stimulator, lipopolysaccharide, or anti-IgM plus IL-4. These results indicate that the primary cellular target of ddI is the B lymphocyte. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    0041-008X
  • Document Type:
  • Genre:
  • Place as Subject:
  • CIO:
  • Division:
  • Topic:
  • Location:
  • Pages in Document:
    260-267
  • Volume:
    145
  • Issue:
    2
  • NIOSHTIC Number:
    nn:20033926
  • Citation:
    Toxicol Appl Pharmacol 1997 Aug; 145(2):260-267
  • Contact Point Address:
    Albert E. Munson, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Road, Morgantown, WV 26505
  • Federal Fiscal Year:
    1997
  • Peer Reviewed:
    True
  • Source Full Name:
    Toxicology and Applied Pharmacology
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:32ff6764a888e1c019d030b1544855748289c2e77e28824424fbbabddb0d536f9d65d47312f37f8b8002de0ea1267399e455c70e60b93441fb38ff12bc04b3cd
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  • File Type:
    Filetype[PDF - 195.61 KB ]
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