Serum colony-stimulating and colony-inhibitory activity in response to neutropenia

Since sera from most species contain both colony-stimulating and column-inhibitory factors, the net CSA results from a balance between these opposing substances. Studies were performed to determine whether the increased CSA noted during neutropenia or endotoxemia is due to an increase in CSF or to a decline in serum inhibitors. Rats were treated with cyclophosphamide, total body irradiation, or endotoxin and bled during the peak CSA response. By separation studies using Sephadex G150, it was shown that serum levels of high-molecular-weight inhibitors were unchanged from control values. Minimal CSA was detected in normal serum fractions; increased activity was found in fractions from neutropenic animals. During a postcyclophosphamide rebound neutrophilia, serum CSA was undetectable; inhibitor levels were similar to those measured in untreated controls. These observations show that the increased serum CSA seen with neutropenia is due to a true increase in CSF and not to a decline in circulating inhibitors.