Cytokine expression profiling in human leukocytes after exposure to hypertonic and isotonic fluids.
BACKGROUND
Resuscitation from hemorrhagic shock causes profound immunologic changes. The tonicity of fluids used for resuscitation clearly influences the immune response. Our study was designed to determine whether isotonic and hypertonic fluids exert their differential effects on immune response by altering the cytokine gene profile of human leukocytes. The cDNA array method was used to profile transcriptional responses after exposure to hypertonic and isotonic fluids.


METHODS
Blood from seven healthy volunteers was incubated for 30 minutes with isotonic (10% dextran-40 and lactated Ringer's [LR] solution) and hypertonic (7.5% hypertonic saline and hypertonic dextran [HTD]) fluids. The volumes of isotonic fluids used were equal to the volume of blood, whereas the volumes of hypertonic fluids were adjusted to keep the salt load identical to the LR group. The cDNA array technique was used to measure the gene expression of 23 common cytokines.


RESULTS
Increased gene transcription of proinflammatory cytokines (interleukin [IL]-1alpha, IL-6, IL-10, and tumor necrosis factor-alpha) as well as others (IL-5, IL-7, and IL-16) was found after incubation with resuscitation fluids. Variances were noted depending on the type of fluid: HTD and LR solution did not induce expression of IL-5, and HTD also did not induce IL-1beta expression. Genes encoding IL-1alpha, IL-6, IL-9, and tumor necrosis factor-alpha had low level baseline expression in leukocytes isolated from unstimulated blood, and their expression increased markedly after exposure to resuscitation fluids. The inducible transcripts included IL-1beta, IL-7, IL-10, and IL-16. However, there was no difference in cytokine expression profile between isotonic and hypertonic fluids.


CONCLUSIONS
Exposure of human leukocytes to resuscitation fluids causes an increase in cytokine gene expressions compared with undiluted blood. This expression profile is largely independent of the type of fluid used.
Gushchin
Vadim
V
Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Stegalkina
Svetlana
S
Alam
Hasan B
HB
Kirkpatrick
John R
JR
Rhee
Peter M
PM
Koustova
Elena
E
D000328:Adult; D016207:Cytokines / Q000187:drug effects* / Q000235:genetics*; D020869:Gene Expression Profiling; D005950:Glucose Solution, Hypertonic / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology* / Q000627:therapeutic use; D007962:Leukocytes / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D012016:Reference Values; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000235:genetics*
D016207:Cytokines; D005950:Glucose Solution, Hypertonic; D007552:Isotonic Solutions