Oxygen free radical and nitric oxide production in single or combined human schistosomiasis and fascioliasis.

The levels of superoxide (O(-)2) and nitric oxide (NO) production by monocytes have been measured in 15 patients with S. mansoni, 15 patients with Fasciola and six patients with combined infection as well as in control group (15). The levels of both radicals were significantly higher in all patient groups than in the control group, indicating that these radicals may have a role in the immunity against such infections. Patients with chronic fascioliasis showed lower level of O(-)2 and NO than those with schistosomiasis. This may be due to the lodging of the mature Fasciola spp. away from the immune system and subsequently decreased amount of antigens reaching the circulation. In combined infection, the levels of these products were at the highest value, due to increased antigenic stimulation and cross reactivity between the two parasites which may have lead to augmented immune response.

Production of pro-inflammatory cytokines (GM-CSF, IL-8 and IL-6) by monocytes from fasciolosis patients.

The production of pro-inflammatory cytokines by monocytes in vitro has been measured in eight patients with acute fasciolosis and 15 patients in the chronic stage of the disease, before and after stimulation by excretory/secretory Fasciola antigen. Results were compared with those of a control group of 12 individuals. The monocytes from patients with acute fasciolosis produced significantly higher levels of GM-CSF, IL-8 and IL-6 as compared to controls. With chronicity, the production of these cytokines was decreased as compared to the acute stage probably due to decreased antigen level in blood. Stimulation of monocytes of healthy control with E/S Fasciola antigen was accompanied with a markedly increased production of pro-inflammatory cytokines, while monocytes from patients with acute or chronic fasciolosis revealed minimal increase in production. This denoted the importance of E/S Fasciola antigen as an activator of monocytes. A second exposure to the same antigen was accompanied with a limited response.

Leishmania major: leishmanicidal activity of activated macrophages by interferon gamma or tumour necrosis factor.

Infective, stationary growth phase metacyclic promastigotes of Leishmania major were introduced to murine peritoneal macrophages and incubated with recombinant murine tumour necrosis factor (TNF) or with interferon gamma (IFN-gamma) in the presence of LPS. The leishmanicidal activity of macrophages was estimated by the visual counting of intracellular parasites as well as by the (3H) thymidine incorporation of the residual parasites. The culture supernatants were also collected for the estimation of nitrite (NO-2) and hydrogen peroxide (H2O2). The results showed that both (TNF) and (IFN-gamma) had a significant leishmanicidal effect, yet it was more pronounced with IFN-gamma. The production of NO-2 and H2O2 were also correlated with the increased leishmanicidal activity in the activated macrophages.

Tumour necrosis factor-alpha (TNF-alpha) in human toxoplasmosis.

Tumour necrosis factor alpha (TNF-alpha) is a cytokine that is secreted by activated macrophages and monocytes. This work studied TNF-alpha level in sera of patients with toxoplasmosis. Twenty eight female patients (12 of whom had obstetric troubles) and 17 healthy controls were the subjects in this work. According to IHA test and detection of IgM antibodies, three groups of patients were defined, group (I) patients with acute infection, group (II) patients with chronic infection and had high antibody titre, group (III) patients with chronic infections and had low antibody titre. Sera from patients as well as controls were tested for their level of immunologically reactive TNF-alpha using enzyme-linked immunosorbant assay (ELISA). TNF-alpha levels in the sera of patients were significantly higher as compared to healthy control group. Acute infection was associated with the highest levels of TNF-alpha indicating that it may play a role in the pathogenesis of acute toxoplasmosis. In chronic infection, the level of TNF-alpha correlated with IHA antibody titre suggesting that, antibodies against T. gondii may participate in TNF-alpha production. It could be concluded that TNF-alpha may contribute to the pathology in acute infection and may play a role in modulating the host's immune defence against T. gondii in chronic infections.

Measurement of respiratory burst of TNF and IL-1 cytokine activated murine peritoneal macrophages challenged with Toxoplasma gondii.

In vitro activation of murine peritoneal macrophages by TNF and IL-I cytokines resulted in significant elevation of respiratory burst (toxic oxygen metabolites) in comparison to inactivated cells when challenged with Toxoplasma gondii. These oxygen metabolites have been known to have microbicidal activity and so, they may be the direct cause of intracellular killing of T. gondii tachyzoites. The level of these oxygen metabolites was measured by chemiluminescence index. A possible biotherapeutic role for TNF and IL-1, through this mechanism, was also emphasized.

Opsonization and intracellular killing of Toxoplasma gondii by human mononuclear phagocytes.

Macrophages and monocytes have been shown to have an important role in the defence mechanism against Taxoplasma gondii infection. Antibodies in the presence of complement have been found capable of killing extracellular T. gondii. This study demonstrated that tachyzoites in the presence of antitoxoplasma antibodies with complement were detected in 39-58% of monocytes that had phagocytosed them and the mean number of Toxoplasma tachyzoites in this group was significantly low one hour post infection, while only 10-25% of monocytes phagocytosed Toxoplasma tachyzoites in absence of antibodies and complement with significant high number of replicated tachyzoites. This indicated that specific antibodies had a strong opsonizing action. Complement alone was weak in increasing the phagocytic activity.

Assessment of interleukin-1 activity of peritoneal macrophages in mice infected with Schistosoma mansoni before and after praziquantel administration.

This work was devoted to clarify the changes in interleukin-1 (IL-1) activity of peritoneal macrophages in mice experimentally infected with S. mansoni before and after praziquantel administration. A significant increase in (IL-1) activity after praziquantel administration was detected. These findings clarify the role of praziquantel in improving the immune state of the infected host.

The chemiluminescent response of macrophages in mice infected with Schistosoma mansoni.

Peritoneal phagocytic cells when stimulated by Schistosoma mansoni infection in this study, exhibited a sudden increase in oxygen consumption known as a respiratory burst. This resulted in the production of toxic oxygen metabolites (H2O2 and others). The level of this toxic oxygen metabolites (chemiluminescence/cells) in normal mice and in mice infected with S. mansoni was measured in vitro. One week, one and two months after infection, a highly significant increase in the levels of chemiluminescence/cell was observed when compared to that of the normal control group. These oxygen metabolites have long been known to have microbicidal activity, and may take part in the ecytotoxic role in cell-mediated immune response against all stages of schistosoma life cycle in this study.