Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide

Neutrophils play a crucial role in the pathogenesis of joint inflammatory diseases such as rheumatoid arthritis (RA). Therefore their elimination and/or a functional inhibition might have beneficial or even therapeutic effects in these diseases. In the present study we exploited the cytotoxic action of etoposide to deplete neutrophils. We administrated the drug twice (at day -3 and day -1) to SCID mice having intact innate immunity and a fail in T- and B-cell maturation. Ankle inflammation was induced by the injection of zymosan (ZY). Joint damage was evaluated by histology grading system for cell infiltration and proteoglycan loss and degree of cartilage erosion. The frequencies of mature Ly6G+CD11b+ cells in bone marrow (BM) were monitored at days -4, -2 and 0 by flow cytometry. At day 7 of ankle inflammation the amounts of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-17 were measured by enzyme-linked immunosorbent assay (ELISA). Histological analysis of the joint sections showed decreased scores for cell infiltration and cartilage proteoglycan loss and reduced cartilage erosion in drug-treated zymosan injected mice in comparison to untreated group with ankle inflammation. Etoposide diminished cell numbers in BM, inhibits granulopoiesis triggered by zymosan and decreased the frequencies of mature Ly6G+CD11b+ cells in BM and eliminated Ly6G+ cells from blood and synovial fluid. We observed reduced TNF-α and impaired IL-17 production in etoposide-treated ZY group. Our data provide a proof-of principle that the elimination of neutrophils might be exploited in a design of new therapeutic approaches for joint inflammatory diseases

Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes.

International audienceSepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single pro-inflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could well be explained by the widespread gene expression dysregulation known as "genomic storm" in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this "storm". Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some pro-inflammatory molecules, complement components and endogenous "danger" signals. The improved survival in endotoxemia was associated with serum levels of pro-inflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes

The Chemical and Biological Properties of Propolis

The term propolis comes from two Greek words, pro (which means for or in defence of) and polis (which means the city); thus, propolis means in defence of the city or beehive. Propolis is a sticky resinous substance, which is gathered from buds and the bark of trees. It is also known as "bee glue" as bees use it to cover surfaces, seal holes and close gaps in their hives, thus providing a sterile environment that protects them from microbes and spore-producing organisms, including fungi and molds. It can be considered to be a potent chemical weapon against bacteria, viruses, and other pathogenic microorganisms that may invade the bee colony. Also, bees use propolis as an embalming substance, to mummify invaders such as other insects, that have been killed and are too heavy to remove from the colony. Thus, propolis is important for bee health but it also has activity against many human diseases. It is a powerful anti-oxidant and can modulate the activity of reactive oxygen species within the human body. The most studied aspect of propolis is its anti-bacterial activity, which is almost always present at a moderate to high level depending on the exact type of propolis. It is in general more active against Gram positive than Gram negative bacteria, but activity against Gram negative bacteria has been observed. Propolis has been found to be active against a range of viruses and also is almost always active against protozoa such as Tryanosoma brucei and Leishmania donovani. Propolis also shows activity against cardiovascular diseases and diabetes and has immunomodulatory effects. Anti-cancer activity has also been observed. In summary, propolis is remarkable for its range of biological activities and for the variety of its chemical composition. It may be of great importance both to bees and humans