PMID- 11700923
OWN - NLM
STAT- MEDLINE
DCOM- 20020410
LR  - 20191105
IS  - 0894-1939 (Print)
IS  - 0894-1939 (Linking)
VI  - 14
IP  - 5
DP  - 2001 Sep-Oct
TI  - Anti-TNF antibody treatment has no positive effect on survival in a model of 
      pneumococcal sepsis in pigs.
PG  - 291-7
AB  - Gram-positive organisms causing sepsis have gained more significance in the past 
      years. Especially patients with acquired immunodeficiency have been shown to be 
      at risk for gram-positive infections. The mortality in Streptococcus pneumoniae 
      bacteremia has been shown to be as high as 20%. Tumor necrosis factor-alpha 
      (TNF-alpha) plays a crucial role in the "sepsis cascade." The previously 
      described positive effect of monoclonal TNF antibody (anti-TNF-mAb) in 
      gram-negative sepsis should be controlled in gram-positive pneumococcal sepsis. 
      In a porcine model, pneumococcal sepsis was induced, and the course and outcome 
      of a group treated with anti-TNF-mAb were compared to those of an untreated 
      control. Streptococcus pneumoniae serotype 6 B was isolated from patients with 
      systemic infection. The isolates were prepared, cryopreserved at -80 degrees C, 
      and recultivated in a standardized fashion as needed. Then 10(9) bacteria were 
      injected intravenously. Pigs of the German Landrace type with a weight of 20-30 
      kg were anesthetized using standardized midazolam and ketamine intravenous 
      anesthesia. After introduction of central venous, arterial, and urinary 
      catheters, bacteria were injected intravenously via the ear vein. In the therapy 
      group, animals were treated with anti-TNF-mAb (5 mg/kg body weight) intravenously 
      immediately prior to pneumococci injection. Survival and survival times were 
      primary endpoints. Biochemical and vital parameters were also compared. In the 
      anti-TNF-mAb group, 4/11 animals died (35%), compared to 6/11 (55%) in the 
      control group. The mean survival times were 11 and 10 h, respectively (n.s.). TNF 
      levels were significantly different. The TNF peak at 90-240 min was not present 
      in the anti-TNF group (340 pg/ml vs. 19 pg/ml, p = .034). Leukocyte counts 
      differed also significantly. After an initial drop in both groups, we observed a 
      leukocytosis of up to 32.8 +/- 5.0 g/L in the anti-TNF-group, while in the 
      control group leukocyte counts remained below 15.0 g/L (13.3 +/- 3.0 g/L, p = 
      .007). All other parameters did not differ significantly. Thus, anti-TNF-mAb 
      effectively suppresses the TNF peak following gram-positive septicemia. In the 
      presented setting, these effects did not influence overall survival or survival 
      times.
FAU - Gawad, K A
AU  - Gawad KA
AD  - Department of General Surgery, Eppendorf University Hospital, Hamburg, Germany. 
      gawad@uke.uni-hamburg.de
FAU - Schneider, C
AU  - Schneider C
FAU - Brinken, B
AU  - Brinken B
FAU - Huflander, A
AU  - Huflander A
FAU - Diederichs, B
AU  - Diederichs B
FAU - Mack, D
AU  - Mack D
FAU - Gutensohn, K
AU  - Gutensohn K
FAU - Izbicki, J R
AU  - Izbicki JR
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Invest Surg
JT  - Journal of investigative surgery : the official journal of the Academy of 
      Surgical Research
JID - 8809255
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Disease Models, Animal
MH  - Leukocyte Count
MH  - Pneumococcal Infections/mortality/*therapy
MH  - Sepsis/mortality/*therapy
MH  - Survival Rate
MH  - Swine
MH  - Tumor Necrosis Factor-alpha/*immunology/metabolism
EDAT- 2001/11/10 10:00
MHDA- 2002/04/11 10:01
CRDT- 2001/11/10 10:00
PHST- 2001/11/10 10:00 [pubmed]
PHST- 2002/04/11 10:01 [medline]
PHST- 2001/11/10 10:00 [entrez]
AID - 10.1080/089419301753170075 [doi]
PST - ppublish
SO  - J Invest Surg. 2001 Sep-Oct;14(5):291-7. doi: 10.1080/089419301753170075.