Gram-negative bacteria killed by complement are associated with more severe biliary infections and produce more tumor necrosis factor-alpha in sera.
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.
Stewart
Lygia
L
Department of Surgery, University of California San Francisco, USA.
Oesterle
Adair L
AL
Griffiss
J McLeod
JM
Jarvis
Gary A
GA
Aagaard
Beverly
B
Way
Lawrence W
LW
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*
D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins