title: Gram-negative bacteria killed by complement are associated with more severe biliary infections and produce more tumor necrosis factor-alpha in sera.
abstract: BACKGROUND
  We previously showed that gallstones contain bacteria and that illness severity correlates with bacterial presence. This study examined virulence differences of gram-negative biliary bacteria.
  
  
  METHODS
  Gallstones and bile were cultured, and sera obtained, from 210 patients. Infection severity was staged as: none-no clinical infection; moderate-fever, leukocytosis; or severe-bacteremia, cholangitis, hypotension, abscess, or organ failure. Gram-negative biliary bacteria were tested against patient (and control) serum for complement-mediated bacterial killing and induction of tumor necrosis factor-alpha (TNFalpha) production (using cultured monocytes) with and without sera. These results were correlated with infection severity.
  
  
  RESULTS
  A total of 98 (47%) patients had biliary bacteria. Infection severity distribution was none, 29%; moderate, 35%; and severe, 36%. Gram-negative organisms killed by complement were associated with more severe infections as follows: 13%, none; 60%, moderate; and 88%, severe infections (P =.024 and P <.0001, respectively vs none, chi-square test). TNFalpha production in sera increased 182 pg/mL with complement resistant bacteria, but increased 546 pg/mL with bacteria killed by complement (P <.0001, killed vs not killed, Student's t test). E coli and Klebsiella were the most virulent bacterial species. They were cultured from blood, usually killed by complement, and had the largest increase in TNFalpha production in sera.
  
  
  CONCLUSIONS
  Gram-negative biliary bacteria killed by complement (as opposed to complement-resistant) were associated with more serious biliary infections including bacteremia and induced more TNFalpha production in sera. This suggests a potential role for complement activation and cytokine production in biliary sepsis.
authors.affiliation: Department of Surgery, University of California San Francisco, USA.
authors.forename: Lygia
authors.initials: L
authors.lastname: Stewart
authors.forename: Adair L
authors.initials: AL
authors.lastname: Oesterle
authors.forename: J McLeod
authors.initials: JM
authors.lastname: Griffiss
authors.forename: Gary A
authors.initials: GA
authors.lastname: Jarvis
authors.forename: Beverly
authors.initials: B
authors.lastname: Aagaard
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Way
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001659:Biliary Tract / Q000276:immunology* / Q000382:microbiology; D002769:Cholelithiasis / Q000276:immunology / Q000382:microbiology; D003167:Complement Activation / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D006090:Gram-Negative Bacteria / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins