Circadian rhythm of granulocyte-macrophage colony-stimulating factor in normal subjects and neutropenic hospitalised patients.

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of the haemopoietic growth factors, has rarely been detected in human serum. It has, therefore, been suggested that a paracrine model can explain its behaviour where the substance is produced and acts locally. An alternative explanation might be due to blood sampling time with GM-CSF concentrations undetectable at the nadir of secretion. HYPOTHESIS: We hypothesised that endogenous production of GM-CSF in humans is subject to diurnal rhythm. METHODS: Blood samples were obtained from 17 healthy individuals and 17 neutropenic hospitalised patients with haematological malignancies on myelosuppressive therapy at 6, 12, 18 and 24 hours. In the neutropenic patients, samples were collected at the nadir of the neutrophil count (ANC < 0.2 x 109/L). Serum was assayed for GM-CSF levels using an enzyme-linked immunosorbent assay method. RESULTS: There were significant differences in the mean levels of GM-CSF within the two groups (P < 0.001). In normal subjects, peak GM-CSF levels were reached at six hours (mean = 10.1 pg/ml). Peak levels were reached in hospitalised neutropenic patients at 18 hours (mean = 13.7 pg/ml). The difference between the peak GM-CSF levels in the two groups was not significant (P = 0.11). On factorial design analysis, there was a significant interaction between the time of blood collection and the subject groups (P < 0.001). CONCLUSIONS: Our data are consistent with a diurnal secretion pattern for GM-CSF in both normal and neutropenic patients. As this finding might have practical implications, including timing of administration of GM-CSF in neutropenic patients, further studies are suggested.