||Host Resistance to Murine Malaria in Mice Exposed to the Adenosine Deaminase Inhibitor, 2'-Deoxycoformycin.
Luebke, R. W. ;
Andrews, D. L. ;
Copeland, C. B. ;
Riddle, M. M. ;
Rogers, R. R. ;
||Health Effects Research Lab., Research Triangle Park, NC. ;Northrop Services, Inc., Research Triangle Park, NC.
Adenosine deaminase ;
Host-parasite relations ;
Natural killer cells ;
Antibody formation ;
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||Resistance to infection with the nonlethal rodent malaria parasite Plasmodium yoelii 17XNL (Py17XNL) is mediated by humoral, T-cell and accessory cell activity. The purpose of the study was to profile host resistance to infection with this organism in mice exposed to 2-deoxycoformycin (2dCF), a potent adenosine deaminase (ADA) inhibitor. Inhibition of ADA activity by 2dFC results in defective T-cell function and either suppression or augmentation of the humoral response, depending on whether 2dCF exposure precedes (suppression) or follows (augmentation) immunization. In the study, mice injected with 2dCF during the first five days of infection cleared the infection at the same time as controls, but had lower peak parasitemia than controls. Mice infected with the lethal variant of P. yoelii were more susceptible to infection when injected with 2dCF after infection, suggesting that 2dCF injection did not directly affect the parasite. Rather, suppression of parasitemia in 2dCF-treated mice may have been mediated by augmented humoral immunity, since 2dCF injection increases antibody responses when 2dCF injection follows antigen (in this case, parasite) injection. Conversely, in mice given 2dCF prior to infection, parasitemia peaked 2 days later and was eliminated more gradually than in control mice. These results indicate that 2dCF, given before or after infection, alters the host response to infection with Py17XNL. It appears that a combination of increased macrophage activity and altered T-cell activity contributed to the delay in peak parasitemia and clearance of infection in mice exposed to 2dCF before infection with Py17XNL.
||Pub. in International Jnl. of Immunopharmacology, v13 n7 p987-997 Oct 91. See also PB84-238666, PB85-198810 and PB89-105688. Prepared in cooperation with Northrop Services, Inc., Research Triangle Park, NC.
|NTIS Title Notes
||Reprint: Host Resistance to Murine Malaria in Mice Exposed to the Adenosine Deaminase Inhibitor, 2'-Deoxycoformycin.
||57N; 57Q; 57J
||PC A03/MF A01