title: The effect of TIP on pneumovirus-induced pulmonary edema in mice.
abstract: BACKGROUND
  Pulmonary edema plays a pivotal role in the pathophysiology of respiratory syncytial virus (RSV)-induced respiratory failure. In this study we determined whether treatment with TIP (AP301), a synthetic cyclic peptide that mimics the lectin-like domain of human TNF, decreases pulmonary edema in a mouse model of severe human RSV infection. TIP is currently undergoing clinical trials as a therapy for pulmonary permeability edema and has been shown to decrease pulmonary edema in different lung injury models.
  
  
  METHODS
  C57BL/6 mice were infected with pneumonia virus of mice (PVM) and received TIP or saline (control group) by intratracheal instillation on day five (early administration) or day seven (late administration) after infection. In a separate set of experiments the effect of multiple dose administration of TIP versus saline was tested. Pulmonary edema was determined by the lung wet-to-dry (W/D) weight ratio and was assessed at different time-points after the administration of TIP. Secondary outcomes included clinical scores and lung cellular response.
  
  
  RESULTS
  TIP did not have an effect on pulmonary edema in different dose regimens at different time points during PVM infection. In addition, TIP administration did not affect clinical severity scores or lung cellular response.
  
  
  CONCLUSIONS
  In this murine model of severe RSV infection TIP did not affect pulmonary edema nor course of disease.
authors.affiliation: Pediatric Intensive Care Unit, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Elske
authors.initials: E
authors.lastname: van den Berg
authors.affiliation: Pediatric Intensive Care Unit, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Reinout A
authors.initials: RA
authors.lastname: Bem
authors.affiliation: Pediatric Intensive Care Unit, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert P
authors.initials: AP
authors.lastname: Bos
authors.affiliation: Department of Respiratory Medicine and Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Pediatric Intensive Care Unit, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Job B M
authors.initials: JB
authors.lastname: van Woensel
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D029122:Murine pneumonia virus / Q000187:drug effects / Q000302:isolation & purification*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000627:therapeutic use*; D018186:Pneumovirus Infections / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry
chemical_list: D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C583752:AP301 peptide