concanavalin-a and Leukopenia

We investigated the immunohematoxicities of the antiparasitic drug dapsone (DDS) and the antiretroviral drug zidovudine (ZDV, AZT) given alone or in combination in BALB/c mice. DDS is used for prophylaxis and treatment of Pneumocystis carinii infection in AIDS patients. We examined the impact of concurrent administration of these drugs on the immune and hematopoietic systems because DDS causes hematotoxicity and ZDV therapy results in bone marrow toxicity. Daily oral administration of DDS at 25 and 50 mg/kg for 28 days caused a slight anemia, marked methemoglobinemia, reticulocytosis, and a moderate leukopenia (P < 0.01 for all parameters) but had no discernible effect on platelet count. In DDS-treated mice, the proliferative response of splenic T cells to concanavalin A was > or = 35% higher than that manifested by splenocytes from vehicle-treated control mice. ZDV at 240 and 480 mg/kg was not immunosuppressive but caused low-grade macrocytic anemia, thrombocytosis, and neutropenia; these effects were drug dose-dependent and statistically significant (P < 0.01). Concurrent administration of DDS and ZDV augmented the severity of ZDV-mediated macrocytic anemia, and 7 of 12 (58%) mice did not survive treatment with the high doses of DDS and ZDV (50 and 480 mg/kg, respectively). On the other hand, co-administration of ZDV mitigated DDS-induced methemoglobinemia and the DDS-associated elevation in lymphoproliferative response. These data suggest interaction between DDS and ZDV in mice and indicate a need for caution in using DDS as long-term therapy in AIDS patients receiving ZDV.

Topics: AIDS-Related Opportunistic Infections; Anemia; Animals; Anti-HIV Agents; Antiprotozoal Agents; Bone Marrow; Concanavalin A; Dapsone; Dose-Response Relationship, Drug; Drug Interactions; Female; Leukopenia; Lymph Nodes; Lymphocyte Activation; Methemoglobinemia; Mice; Mice, Inbred BALB C; Neutropenia; Pneumonia, Pneumocystis; Thrombocytosis; Thymus Gland; Zidovudine

The present study evaluated the immunomodulatory effect of the administration of different intensities of electric foot shock presentations to different strains of mice. The results showed an enhancement of the mitogenic responsiveness to concanavalin A (Con A), a T-lymphocyte mitogen, that was directly related to the intensity of the electric shock presentations. However, the electric shock induced no significant alteration of the mitogenic responsiveness to lipopolysaccharide (LPS), a B-lymphocyte mitogen. These findings were evident in HLA-SW/ICR, C57BL/6N, and C3H/HEJ mice. In contrast, the C3H/HEN mice did not show any alteration of mitogenic responsiveness. The number of splenic leukocytes was not altered by the electric shock presentations in the strains that showed enhanced mitogenic responsiveness, but the C3H/HEN strain showed a leukopenia directly related to the shock intensity. In a subsequent experiment, it was demonstrated that repeated sessions of electric shock resulted in a reduction in the enhancement effect. Collectively, the results demonstrate that stressful stimulation can result in an enhancement of mitogenic responsiveness, but that such an effect is dependent on the intensity and frequency of the stressor, as well as on the strain of the subject.

Topics: Animals; Concanavalin A; Electroshock; Leukopenia; Lipopolysaccharides; Lymphocyte Activation; Male; Mice; Mice, Inbred Strains; Stress, Physiological