concanavalin-a and Anemia

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

Infection of mice with African trypanosomes leads to a severe immunosuppression, mediated by suppressor macrophages. Using ex vivo macrophage culture and in vivo cell transfer, it has been shown that nitric oxide (NO) is a potent effector product of these cells and causes both lymphocyte unresponsiveness and dyserythropoiesis. We explored the role of NO in vivo during trypanosome infection using mice with a disrupted interferon-gamma-receptor gene, which were unable to respond with macrophage activation and NO synthesis. These mice were less effective at controlling parasitaemia than the wild types, but showed an improved splenic T-cell responsiveness and reduced anaemia during the early stages of infection. The data indicate that, in the mouse, NO is a significant mediator of immunosuppression only in early infection. Beyond day 10 of infection, NO-independent mechanisms are of primary significance and the control of parasitaemia and T-cell responsiveness are not directly related.

Topics: Anemia; Animals; Cells, Cultured; Concanavalin A; Female; Interferon-gamma; Lymphocyte Activation; Macrophages; Mice; Mice, Knockout; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Receptors, Interferon; T-Lymphocytes; Trypanosomiasis, African

Infection of animals with oncogenic viruses frequently leads to an immunosuppressed state. We have examined immunosuppression induced by an avian osteopetrosis virus, myeloblastosis-associated virus of subgroup B inducing osteopetrosis [MAV-2(O)], and our results suggest that this virus induces immunosuppression by a novel mechanism. Lymphoid cells from osteopetrotic chickens did not respond to a wide dose range of concanavalin A (Con A) over a wide cell density range. Failure to undergo blastogenesis was not due to a lack of Con A-binding sites, since 125I-labeled Con A bound to lymphocytes from infected and uninfected chickens. Infected lymphocytes failed to respond to sodium metaperiodate stimulation, indicating that failure of blastogenesis was not due to a blockage of Con A receptor sites. MAV-2(O) infection of chicks 8 days of age resulted in a transient immunosuppression which appeared 1 to 2 weeks after infection. Cell-mixing experiments showed that MAV-2(O)-induced immunosuppression was not attributable to suppressor cells. In contrast, adherent cells from normal lymphoid preparations restored mitogenicity to lymphocytes from MAV-2(O)-infected animals. Adherent cells were present in the spleen and peripheral blood lymphocytes of MAV-2(O)-infected chickens in numbers comparable to those of the uninfected animal, and both sets of cells contained Fc-dependent phagocytic activity and nonspecific esterase. Peritoneal exudate cells were elicited from osteopetrotic and normal chickens in similar numbers. We conclude that MAV-2(O) induces immunosuppression by interfering with an accessory function of macrophage-like adherent cells.

Topics: Anemia; Animals; Avian Leukosis; Avian Myeloblastosis Virus; Chickens; Concanavalin A; Immune Tolerance; Lymphocyte Activation; Macrophages; Osteopetrosis; Receptors, Concanavalin A; Satellite Viruses; T-Lymphocytes, Regulatory

Topics: Anemia; Animals; Biological Assay; Bone Marrow; Bone Marrow Cells; Cell Division; Cells, Cultured; Chromatography, Affinity; Chromatography, Gel; Clone Cells; Concanavalin A; Culture Media; Erythrocytes; Erythropoietin; Humans; Male; Methods; Methylcellulose; Mice; Polysaccharides