Systemic inflammation like in sepsis is still lacking specific diagnostic markers and effective therapeutics. The first line of defense against intruding pathogens and endogenous damage signals is pattern recognition by e.g., complement and Toll-like receptors (TLR). Combined inhibition of a key complement component (C3 and C5) and TLR-co-receptor CD14 has been shown to attenuate certain systemic ...

Immunological abnormalities have been demonstrated in several psychiatric disorders. Predominantly, studies have focused on younger adults, and research on elderly psychiatric in-patients is scant. In this naturalistic study, we investigated changes in cytokine levels during the treatment of diagnostically unselected elderly psychiatric in-patients, and whether these changes could be related to ...

Cholesterol crystals are known to be a hallmark of atherosclerosis with recent studies demonstrating deposition of these crystals in early fatty streak formation as well as penetrating the intima following plaque rupture. Inflammation has also become a central focus in atheroma development and endothelial cell activation is recognized as necessary for the recruitment of inflammatory cells to the ...

Inadequate supplies of donor corneas have evoked an escalating interest in corneal xenotransplantation. However, innate immune responses contribute significantly to the mechanism of xenograft rejection. We hypothesized that complement component C5 and TLR co-receptor CD14 inhibition would inhibit porcine cornea induced innate immune responses. Therefore, we measured cytokine release in human blood, ...

Background<br> Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis.<p> Methods ...

Introduction: Sepsis is an exaggerated and dysfunctional immune response to infection. Activation of innate immunity recognition systems including complement and the Toll-like receptor family initiate this disproportionate inflammatory response. The aim of this study was to explore the effect of combined inhibition of the complement component C5 and the Toll-like receptor co-factor CD14 on survival, ...

<i>Background</i>- It remains uncertain whether activation of the complement system, assessed by the soluble terminal C5b‐9 complement complex (plasma TCC), is associated with future risk of incident venous thromboembolism (VTE).<p> <p><i>Objectives</i>- To investigate the association between plasma levels of TCC and future risk of incident VTE in a nested case‐control study, and to explore ...

Catastrophic antiphospholipid syndrome is associated with excessive complement activation explaining the clinical efficacy of complement inhibitory treatment.

We found that compstatin, which inhibits the cleavage of complement component C3 to its components C3a and C3b, reduced the E. coli-induced platelet aggregation by 42%-76% (p = 0.0417). This C3-dependent aggregation was not C3a-mediated as neither inhibition of C3a using a blocking antibody or a C3a receptor antagonist, nor the addition of purified C3a had any effects. In contrast, a C3b-blocking ...

Inhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized ...