Potassium-inhibited processing of IL-1 beta in human monocytes.

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Abstract
Agents that deplete cells of K+ without grossly disrupting the plasma membrane were found to stimulate the cleavage of pro‐interleukin (IL)‐1 beta to mature IL‐1 beta. Agents examined in this study included staphylococcal alpha‐toxin and gramicidin, both of which selectively permeabilize plasma membranes for monovalent ions, the ionophores nigericin and valinomycin, and the Na+/K+ ATPase inhibitor ouabain. K+ depletion by brief hypotonic shock also triggered processing of pro‐IL‐1 beta. The central role of K+ depletion for inducing IL‐1 beta maturation was demonstrated in cells permeabilized with alpha‐toxin: processing of pro‐IL‐1 beta was totally blocked when cells were suspended in medium that contained high K+, but could be induced by replacing extracellular K+ with Na+, choline+ or sucrose. To test whether K+ flux might also be important in physiological situations, monocytes were stimulated with lipopolysaccharide (LPS) for 1‐2 h to trigger pro‐IL‐1 beta synthesis, and transferred to K(+)‐rich medium. This maneuver totally suppressed IL‐1 beta maturation. Even after 16 h, however, removal of K+ from the medium resulted in rapid processing and export of IL‐1 beta. Ongoing export of mature IL‐1 beta from cells stimulated with LPS for 2‐6 h could also be arrested by transfer to K(+)‐rich medium. Moreover, a combination of two K+ channel blockers inhibited processing of IL‐1 beta in LPS‐stimulated monocytes. We hypothesize that K+ movement and local K+ concentrations directly or indirectly influence the action of interleukin‐1 beta‐converting enzyme (ICE) and, possibly, of related intracellular proteases.