Cytokine priming of the granulocyte respiratory burst in myelodysplastic syndromes

Increased susceptibility to infections in patients with myelodysplastic syndromes (MDS) is thought to be due to neutropenia as well as functional abnormalities of neutrophils. In the present study we examined the effect of two different stimulants (fMLP, PMA) and three cytokines (alpha TNF, G-CSF and GM-CSF), both singly and in combination on granulocyte (RB) in 25 MDS patients compared to seven healthy controls; Single fMLP and PMA-stimulation showed similar results for both groups. Preincubation with cytokines enhanced fMLP-stimulated RE in most MDS patients and controls, but in patients to a significantly lesser extent when compared to the control group (p less than or equal to 0,05). Combinations of alpha TNF + GM-CSF and alpha TNF + G-CSF were highly synergistic in priming fMLP-stimulated burst in both groups. But again, as with the single cytokine priming this effect was markedly reduced in MDS patients compared to controls (p less than or equal to 0,05). A specific priming defect for one of the cytokines or a cytokine combination could not be demonstrated. Serum alpha TNF levels were measured in 18 and neutrophil alkaline phosphatase (NAP) index in 23 patients. Results did not correlate with variations of the RE in MDS patients. We conclude that reduced alpha TNF, GM-CSF and G-CSF priming of granulocyte RE is a frequent finding in MDS and may contribute to the enhanced susceptibility to bacterial infections.