Neutrophiia-inducing Activity in Plasma of Neutropenic Human Beings

Humoral factors have been implicated in the bone marrow release of neutrophils in experimental animals in response to neutropenia. No comparable studies have yet been reported in man, although a humoral mechanism has been described in the neutrophilic response to endotoxin. Three patients with reversible drug-induced neutropenia were studied for the presence of neutrophilia-inducing activity by obtaining plasma during neutropenia and after recovery. When the blood neutrophil concentration and marrow granulocyte reserves were normal, the paired plasmas were returned to the donors on different days, and the blood neutrophil concentrations sequentially measured. Reinfusion of the plasmas obtained from the two patients with marked neutropenia was associated with a 2.5-3.5-fold increase in the total neutrophil concentration and an 8.5-fold increase in the nonsegmented neutrophils, with the peak 30-60 min after infusion. In contrast, plasma obtained when the blood neutrophil concentration was normal did not have this effect. Plasma from the patient with only slight neutropenia was not associated with neutrophilia-inducing activity. Neutrophilia-inducing activity is present in increased concentration in the plasma of severely neutropenic human beings and we suggest that it plays a role in regulating the blood neutrophil concentration by causing release of neutrophils from the bone marrow.