title: Anti-TNF antibody treatment has no positive effect on survival in a model of pneumococcal sepsis in pigs.
abstract: 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.
authors.affiliation: Department of General Surgery, Eppendorf University Hospital, Hamburg, Germany. gawad@uke.uni-hamburg.de
authors.forename: K A
authors.initials: KA
authors.lastname: Gawad
authors.forename: C
authors.initials: C
authors.lastname: Schneider
authors.forename: B
authors.initials: B
authors.lastname: Brinken
authors.forename: A
authors.initials: A
authors.lastname: Hufländer
authors.forename: B
authors.initials: B
authors.lastname: Diederichs
authors.forename: D
authors.initials: D
authors.lastname: Mack
authors.forename: K
authors.initials: K
authors.lastname: Gutensohn
authors.forename: J R
authors.initials: JR
authors.lastname: Izbicki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D007958:Leukocyte Count; D011008:Pneumococcal Infections / Q000401:mortality / Q000628:therapy*; D018805:Sepsis / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha