Hypertonic immunomodulation is reversible and accompanied by changes in CD11b expression

Background. In a two-hit model of hemorrhagic shock and lipopolysaccharide (LPS), we previously showed that hypertonic saline (HTS) resuscitation redu ced lung sequestration of neutrophils and the accompanying injury. This eff ect was partially attributed to suppressed expression of the surface adhesi on molecule CD11b. This study investigates the duration of this protective effect after a single HTS dose and the usefulness of repeated infusions. Material and Methods. The previous two-hit rodent model was used. Neutrophi l lung sequestration was measured by bronchoalveolar fluid cell count. CD11 b expression was followed by flow cytometry. In vitro studies used isolated human neutrophils. Results. Eighteen hours following resuscitation, the protective effect of H TS was lost. At this time, LPS caused an increase in both neutrophil lung s equestration and CD11b expression, regardless of the resuscitation regimen used. A second infusion of HTS prevented these changes and restored the lun g protection observed earlier. In vitro studies showed that the duration of hypertonic pretreatment is an important determinant of cell responsiveness under the isotonic conditions: Four but not 2 h hypertonic exposure was ab le to prevent upregulation of CD11b induced by LPS added immediately after reestablishing isotonicity. Conclusions. This study demonstrates that HTS resuscitation lessens lung ne utrophil sequestration and CD11b surface expression induced by LPS. This pr otective effect is transient but can be restored by a second HTS infusion s uggesting that maintenance of beneficial effect necessitates repeated HTS a ddition. The reversibility ensures rapid modulation of neutrophil functions , thereby preventing acute tissue damage without causing long-lasting immun osuppression. (C) 1999 Academic Press.