Sodium chloride inhibits cytokine production by lipopolysaccharide-stimulated human neutrophils and mononuclear cells.

Hypertonic sodium chloride (NaCl) solution has been shown to have beneficial effects on patients with hypovolemic shock. Therapy with hypertonic saline seems to neutralize or minimize the deleterious immune responses in these patients. In this study, we addressed how hypertonic NaCl solution affects the release of cytokines by isolated human blood cells. We examined the effect of NaCl on tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-1beta, and IL-1 receptor antagonist released by human neutrophils and mononuclear cells under nonstimulated and LPS-stimulated conditions. Cells isolated from healthy donors were cultured in the presence or absence of lipopolysaccharide (LPS). Cytokine concentrations were measured by enzyme-linked immunosorbent assay in culture supernatants. The addition of NaCl lowered the production of IL-8, TNF-alpha, and IL-1 receptor antagonist by neutrophils, and IL-8 and IL-1beta by mononuclear cells stimulated with LPS. This effect was not observed when NaCl solution was replaced by a solution of potassium iodide in the same conditions. The decreased production of cytokines in the presence of hypertonic saline was not caused by cell death. Our findings support the proposal that the modulation of leukocyte inflammatory response by NaCl occurs by an electrolyte-specific effect in addition to the hyperosmolarity. Furthermore, the results of this study support the therapeutic use of appropriate doses of i.v. NaCl solutions to minimize tissue injury characterized by neutrophil and mononuclear cell infiltration into tissues in post-traumatic patients.