Delayed neutralization of interferon-gamma prevents lethality in primate Gram-negative bacteremic shock.

Objective: Whether anticytokine therapies have a place in the treatment of severe sepsis and septic shock remains a question. Although a number of preclinical studies have shown efficacy in primate models of bacteremic shock when administered prophylactically, these same therapies have a significantly diminished effectiveness when administered therapeutically. This study investigated whether delayed administration of a novel anti-human interferon-gamma monoclonal antibody could improve outcome and reduce organ injury in a lethal model of Escherichia coli bacteremia, when administered after the onset of shock.

Increased lymphoid tissue apoptosis in baboons with bacteremic shock.

The molecular mechanisms of immune cell apoptosis during sepsis remain unclear. Two young adult baboons (Papio sp.) received a lethal dose of live Escherichia coli and were sacrificed at either 16 (for animal welfare concerns) or 24 h post-septic shock.

Association of rapamycin and co-stimulation blockade using anti-B7 antibodies in renal allotransplantation in baboons.

Background: Co-stimulation blockade has already been shown to induce transplantation tolerance in rodents, but until now has failed in large animal models. We therefore sought to investigate whether the addition of rapamycin to a co-stimulation blockade regimen could induce tolerance in baboon recipients of a renal allograft and to characterize the immunological characteristics of rejection.

Methods: Two baboons were used for a pharmacological and toxicological analysis and received anti-B7.

Use of in Vitro Correlates for Selection of Candidate Immunosuppressive Antibodies Prior to a Primate Transplant Model.

The selection of possible candidate immunosuppressive antibodies to prevent graft rejection is performed in vitro. Additionally, due to the species specificity of these monoclonal antibodies (MABs), pre-clinical studies in non-human primates are necessary. If a positive correlation between the in vitro and in vivo findings would exist, these tests can act as a pre-screening before new reagents are tested in vivo.