Cyclic neutropenia and T lymphocyte suppression of granulopoiesis: abrogation of the neutropenic cycles by lithium carbonate.

To investigate the mechanisms of cyclic neutropenia, we studied the capacity of a patient's T lymphocytes (TLp) to interact with monocyte-macrophages from her normal HLA-identical sibling (MOb) in the elaboration of colony-stimulating activity (CSA). TLp obtained at the time of decreasing neutrophil counts, increased CSA elaboration (p less than 0.056) when incubated at a 1:1 ratio with MOb. Increasing the TLp to MOb ratios to 3:1 or 5:1 progressively decreased CSA. Also, lithium carbonate, which ordinarily prevents concanavalin A activation of suppressor TL, failed to do so, suggesting that preactivated suppressor TL were present in the patient while neutrophil levels were falling. In similar experiments performed while neutrophil levels were rising these activated suppressor TL were absent. These data suggest that some patients with cyclic neutropenia may have a cyclic increase in suppressor TL activity. As predicted by our in vitro experiments, lithium carbonate administration did not abrogate the first neutropenic cycle, but it did mitigate subsequent cycles.