Clinical benefits of improving host defences with rHuG-CSF

Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) has been shown to stimulate the production and function of neutrophils in vitro and in vivo. Clinical studies in patients receiving myelosuppressive chemotherapy showed earlier neutrophil recovery, a reduction in infectious complications of neutropenia, and the use of fewer antibiotics. Its use has also been established for mitigating the infectious complications associated with severe chronic neutropenia (SCN). Data are emerging that neutropenia also contributes to the risk of infections in patients with acquired immunodeficiency syndrome (AIDS) and in neonates with presumed sepsis, and that rHuG-CSF may be a useful adjunct therapy in these patients. More recent studies have focused on enhancing neutrophil number and function in patients with infections not associated with neutropenia. These studies were approached cautiously because of the suggestion that neutrophils might non-selectively amplify the body's inflammatory response in the immunocompetent host and lead to inadvertent tissue injury. Preclinical models have provided a strong rationale for clinical studies to determine whether rHuG-CSF lessens the severity or duration of serious infections or their complications in patients with suboptimal outcome from antibiotics. These studies suggest that elevation of neutrophil levels in these settings is not only safe but has clinical benefit.