A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.

Background: Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α.

Objective: The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy.

Design: Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study.

A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome.

Background: Renin-angiotensin system (RAS) signaling and angiotensin-converting enzyme 2 (ACE2) have been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). We postulated that repleting ACE2 using GSK2586881, a recombinant form of human angiotensin-converting enzyme 2 (rhACE2), could attenuate acute lung injury.

Methods: We conducted a two-part phase II trial comprising an open-label intrapatient dose escalation and a randomized, double-blind, placebo-controlled phase in ten intensive care units in North America.

Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial.

Background: Approximately 5% to 10% of asthmatic patients achieve incomplete symptom control on current therapies. The association of IL-13 with asthma pathology and reduced corticosteroid sensitivity suggests a potential benefit of anti-IL-13 therapy in refractory asthma. GSK679586, a humanized mAb, inhibits IL-13 binding to both IL-13 receptor α1 and α2.

Identification of a putative intracellular allosteric antagonist binding-site in the CXC chemokine receptors 1 and 2.

The chemokine receptors CXCR1 and CXCR2 are G-protein-coupled receptors (GPCRs) implicated in mediating cellular functions associated with the inflammatory response. Potent CXCR2 receptor antagonists have been discovered, some of which have recently entered clinical development. The aim of this study was to identify key amino acid residue differences between CXCR1 and CXCR2 that influence the relative antagonism by two compounds that have markedly different chemical structures.