Inhibitory activity of anti-interleukin-4 and anti-interleukin-10 antibodies on Toxoplasma gondii proliferation in mouse peritoneal macrophages cocultured with splenocytes from infected mice.

Cocultures of splenocytes from Toxoplasma gondii-immunized mice or from naive mice, separated by a transwell membrane from naive macrophage layers, induced a decrease in T. gondii proliferation in macrophages in comparison with cultures without splenocytes or cocultures with splenocytes from infected mice. Interleukin 4 (IL-4) and IL-10 levels increased in cocultures of splenocytes from infected mice with naive macrophages. In contrast, the levels of these cytokines decreased in cocultures with splenocytes from immunized mice. No correlation was found between the release of interferon-gamma (IFN-gamma) and the inhibition of parasite multiplication. Cocultures with splenocytes from immunized mice induced an increase in tumor necrosis factor-alpha (TNF-alpha) levels. In contrast, in cocultures with splenocytes from infected mice, TNF-alpha production decreased. In cocultures with splenocytes from infected mice, T. gondii proliferation in macrophages was neutralized by anti-IL4 or anti-IL10 antibodies and was associated with increased TNF-alpha production. Moreover, this study demonstrates the significant combined effect of IL-4 and IL-10 on the down-regulation of macrophage-effector functions. A soluble positive signal was given by splenocytes to induce the production of TNF-alpha by macrophages. This signal was inhibited by IL4 and IL10. This process is biologically relevant in the regulation of T. gondii proliferation.

Parasitemia and parasitic loads in acute infection and after anti-gamma-interferon treatment in a toxoplasmic mouse model.

Toxoplasma gondii infection was induced in Swiss-Webster mice by intraperitoneal inoculation of avirulent Beverley strain cysts. We studied parasitemia and parasitic loads first in acute toxoplasmosis, then in the chronic stage of the disease. In the latter stage a group of mice received weekly administration of a rabbit antiserum directed against mouse gamma-interferon. Parasitemia, sequentially determined by amplification of the B1 gene using polymerase chain reaction, persisted for more than 1 month in acute toxoplasmosis. Brain and lung parasitic loads, assessed by a tissue-culture method, were significantly increased in mice treated with anti-interferon. Moreover, this increase was prevented by concomitant administration of pyrimethamine and sulfadiazine, suggesting that early prophylaxis would be suitable. Surprisingly, the anti-interferon treatment induced neither abnormal clinical signs nor a significant rise in the parasitemia level. Such a model seems to be particularly appropriate for the comparison of different strains of Toxoplasma gondii in a moderately immunodeficient state.

Aging of the erythrocyte. III. Cation content.

Studies on the main cation content of density-separated bovine erythrocytes showed a progressive decrease in the levels of K+ and Mg2+ with increasing cell density (and age) accompanied by an increase in the level of Na+. The magnitude of net cation loss corresponded to that of red cell volume decrease, but could not account for the total increase in the microviscosity of the erythrocyte interior.