A novel phospholipid-based drug formulation, VP025, modulates age- and LPS-induced microglial activity in the rat.

BACKGROUND: A common change that occurs with age in the central nervous system is an increase in microglial-associated inflammation. This is usually coupled with an increase in the concentration of the inflammatory cytokine interleukin-1beta (IL-1beta) in the hippocampus and an inhibition in long-term potentiation. OBJECTIVES: To assess the effects of a novel preparation of phospholipid nanoparticles incorporating phosphatidylglycerol, VP025, on inflammatory changes in hippocampus of aged and lipopolysaccharide (LPS)-treated rats. METHODS/RESULTS: We report that a possible initial target cell of the putative anti-inflammatory actions of VP025 may be macrophages, as VP025 is engulfed by, and has the capacity to alter the activity of, these cells. VP025 reversed the increase in IFN-gamma concentration in supernatant taken from peritoneal macrophages harvested from LPS-treated rats. In addition, markers of microglial activity, major histocompatibility complex class II (MHC II) mRNA expression, CD40 expression and IL-1beta concentration were increased, and CD200 expression was reduced, in the hippocampus of these rats. VP025 reversed changes in CD40, IL-1beta and CD200 in aged rats, and also restored long-term potentiation in aged and LPS-treated rats. CONCLUSIONS: We conclude that VP025 has the ability to modulate the activity of macrophage, microglia and neurons in response to stressors such as ageing and LPS treatment.

Possible mechanisms underlying age-related resistance to bovine babesiosis.

Calves infected with the tick-borne parasites Babesia spp. do not develop severe clinical babesiosis. Instead they display persistent low parasitaemias without any apparent ill-effects. This age-related resistance not only benefits the host, but also furthers parasite transmission. Both calves and adult animals respond with a Th I immune response to primary infection. Here we hypothesize that the difference in the outcome of infection may at least partly be explained by the localization and timing of the inflammatory response: in calves NO production occurs early and appears to be concentrated in the spleen. On the other hand, there is evidence that a delayed and systemic inflammatory response occurs in adult animals that is ineffectual and probably contributes to the pathogenesis. An improved understanding of the possible mechanisms that underlie this phenomenon may lead to new approaches for the treatment and immune prophylaxis of the disease.

Babesia divergens, a bovine blood parasite of veterinary and zoonotic importance.

Babesia divergens is an intraerythrocytic protozoan parasite, transmitted by the tick Ixodes ricinus, and is the main agent of bovine babesiosis in Europe. It is not only a cause of significant loss to the cattle industry; it can also infect immunocompromised humans, causing medical emergencies characterized by rapid fulmination and parasitemias that may exceed 70%. The current emphasis in Europe on sustainable agriculture and extensification is likely to lead to an increase in vector tick populations with increased risk of infection. Despite the veterinary and zoonotic importance of this parasite, relatively little research has been carried out on B. divergens, and many questions regarding the parasite's epidemiology and the host's response remain unanswered. A better understanding of the species' biology and host-parasite interactions may lead to improved control mechanisms and new trends in vaccine and antibabesial drug development. This review provides the first comprehensive summary of B. divergens biology, including its morphology, life cycle, and host specificity, and the current state of knowledge of both human and bovine infections.