Cacaito would be the one to critique this.
I wonder if and how the millenium molecule relates
>http://www.xoma.com/product_development/cab2.jsp
and then read this
>The Terminal Complement Membrane Attack Complex Is Not Required for Survival from CLP Sepsis: An Anti-C5 Antibody Protects from Mortality in Polymicrobial Sepsis
Lauren Rice, Daniel Orlow, Katherine Ceonzo, Gregory L. Stahl and Jon A. Buras
Beth Israel Deaconess Medical Center: Boston, MA, Brigham and Women's Hospital: Boston, MA
ABSTRACT
OBJECTIVES: Inhibiting complement anaphlytoxin C5a during sepsis may prevent sepsis mortality. Although human anti-C5 antibodies exist, their therapeutic use in microbial sepsis has been avoided because of the hypothesis that inhibiting C5b will prevent formation of the bactericidal membrane attack complex (MAC) and worsen outcome. We wished to test the hypothesis that inhibition of C5 would improve outcomes in sepsis. METHODS:Sepsis was induced in rats by laparotomy and cecal ligation and puncture (CLP) by an IACUC-approved protocol. Sham animals underwent laparotomy without CLP. Following CLP rats were randomized to receive a single iv dose of purified IgG anti-C5 antibody (Ab) or control IgG Ab. Animal survival was noted over 96 hr. In separate experiments, animals were harvested at 24 hr for determining splenic bacterial load and lung injury by myeloperoxidase (MPO) content. Statistical analyses were performed using Log-Rank test and ANOVA. RESULTS: Anti-C5 Ab treated rats (n = 20) had significantly lower mortality vs controls (n = 21), 20 vs. 52% (P = 0.02, Log-Rank). Analysis of bacterial load by culture of spleen homogenates showed a reduction in colony-forming units (CFU) in anti-C5 Ab treated rats (n = 4) vs control IgG (n = 4), 271 ± 381 vs. 2,036 ± 1,106, respectively (P = 0.014). Anti-C5 treatment reduced lung injury as measured by total MPO content of lung tissue as follows: sham (n = 2) 40 ± 30, CLP + IgG (n = 10) 1,320 ± 640, and CLP + anti-C5 (n = 11) 676 ± 608 units MPO/mg of wet tissue weight. Anti-C5 Ab treatment reduced lung MPO vs. IgG control (P = 0.24). Lung MPO contents did not differ between sham and CLP + anti-C5 Ab treated rats, P = 0.19). CONCLUSIONS: Our results show that an anti-C5 antibody therapy prevents CLP sepsis-induced mortality and improves lung injury. Inhibition of the complement MAC does not increase bacterial load or mortality; therefore, the use of anti-C5 therapy may be beneficial rather than detrimental in sepsis. |
