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2',3'-Dideoxyinosine inhibits the humoral immune response in female B6C3F1 mice by targeting the B lymphocyte.

Authors
Phillips-KE; Munson-AE
Source
Toxicol Appl Pharmacol 1997 Aug; 145(2):260-267
NIOSHTIC No.
20033926
Abstract
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.
Keywords
Laboratory-animals; Animal-studies; Immune-system-disorders; Immune-reaction; Immunotoxins; Lymphocytes; Cellular-reactions; HIV; AIDS-virus
Contact
Albert E. Munson, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Road, Morgantown, WV 26505
CODEN
TXAPA9
Publication Date
19970801
Document Type
Journal Article
Fiscal Year
1997
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0041-008X
NIOSH Division
HELD
Source Name
Toxicology and Applied Pharmacology
State
VA; WV
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