title: Local production of CCL3, CCL11, and IFN-γ correlates with disease severity in murine parainfluenza virus infection.
abstract: BACKGROUND
  Using a murine model of parainfluenza virus infection (mPIV1 or Sendai virus; SeV), we compared the inflammatory responses to lethal and sub-lethal infections in inbred DBA/2 mice.
  
  
  METHODS
  Mice were intranasally inoculated with either 1.6×10(3) or 1.6×10(5) infectious units (IU) of SeV or diluent control. Clinical data including daily weights, oxygen saturation, and lung function via whole body plethysmography were collected on days 0, 3-7, and 9-14. Clarified whole lung homogenates were evaluated for inflammatory markers by enzyme-linked immunoassay (ELISA). Data were analyzed using ANOVA or Student t-tests, as appropriate.
  
  
  RESULTS
  Mice inoculated with 1.6×10(5) IU of SeV developed a lethal infection with 100% mortality by day 7, while mice inoculated with 1.6×10(3) IU developed a clinically significant infection, with universal weight loss but only 32% mortality. Interestingly, peak virus recovery from the lungs of mice inoculated with 1.6×10(5) IU of SeV did not differ substantially from that detected in mice that received the 100-fold lower inoculum. In contrast, concentrations of CCL5 (RANTES), CCL11 (eotaxin), interferon-γ, CXCL10 (IP-10), and CCL3 (MIP-1α) were significantly higher in lung tissue homogenates from mice inoculated with 1.6×105 IU (p < 0.05). In the lethal infection, levels of CCL11, interferon- γ and CCL3 all correlated strongly with disease severity.
  
  
  CONCLUSIONS
  We observed that severity of SeV-infection in DBA/2 mice was not associated with virus recovery but rather with the levels of proinflammatory cytokines, specifically CCL11, interferon- γ and CCL3, detected in lung tissue in response to SeV infection.
authors.affiliation: Department of Pediatrics, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA. suryadem@upstate.edu.
authors.forename: Manika
authors.initials: M
authors.lastname: Suryadevara
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Bonville
authors.forename: Helene F
authors.initials: HF
authors.lastname: Rosenberg
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Domachowske
mesh_terms: D000818:Animals; D001835:Body Weight; D054413:Chemokine CCL11 / Q000378:metabolism*; D054405:Chemokine CCL3 / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D010100:Oxygen / Q000097:blood; D018184:Paramyxoviridae Infections / Q000276:immunology* / Q000473:pathology*; D010991:Plethysmography; D012129:Respiratory Function Tests
chemical_list: C515457:Ccl11 protein, mouse; C496534:Ccl3 protein, mouse; D054413:Chemokine CCL11; D054405:Chemokine CCL3; D007371:Interferon-gamma; D010100:Oxygen