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57th Annual Meeting Abstracts


Poster 25

Abstract Title

DMSO Downregulates KC and MIP-2 Chemokine Production During Murine Acute Lung Inflammation

 

Author Block

Kendra Iskander, MD, MPH, Elizabeth Schuller, MA, Jiyoun Kim, PhD, James Becker MD, Daniel Remick, MD

Department of Surgery/Pathology, BostonUniversity School of Medicine, Boston, MA

 

Abstract Body

Background: The in vivo effect of antioxidants such as dimethyl sulfoxide (DMSO) on the cytokine/chemokine expression during inflammatory diseases is largely unclear. In vitro, DMSO will decrease cytokine/chemokine production. We investigated whether DMSO can suppress local chemokine production of murine KC and MIP-2 and diminish neutrophil recruitment after acute lipopolysaccharide (LPS) intra-tracheal challenge.

Methods: Mice were intraperitoneally injected with 20% DMSO in a 0.2 ml volume or normal saline. Ten minutes later, they received 1g LPS by direct intratracheal administration under isoflurane anesthesia. After four hours, bronchoalveolar lavage (BAL) was performed to measure chemokine levels and cytospin preparations were used to determine the total number of pulmonary neutrophils and macrophages.

Results: In the normal saline mice, LPS strongly upregulated both KC and MIP-2 production (see table 1). Increased chemokine production resulted in brisk pulmonary recruitment of neutrophils within the 4 hour study period. Systemic administration of DMSO significantly reduced the BAL concentrations of neutrophil chemoattractants KC and MIP-2 (p<0.01). Decreased chemokines resulted in fewer pulmonary neutrophils (p<0.04) in lungs of DMSO treated mice. Conclusion: Our results show systemic DMSO will downregulate local chemokine production by inhibiting murine KC and MIP-2. Cytokine suppression by DMSO also resulted in diminished neutrophil recruitment in lung inflammation.

 

Normal Saline + LPS

DMSO + LPS

 

Parameter

 

 

P Value

KC

2438 pg/ml 379

284 pg/ml 100

p<0.0001

MIP-2

591 pg/ml 137

90 pg/ml 24

P=0.002

Total Number

of Neutrophils (x 1000)

465 neutrophils 133

157 neutrophils 36

P=0.036

Table 1. Significantly decreased BAL concentrations of KC and MIP-2 chemokines in DMSO treated mice after LPS stimulation. DMSO also caused a significant reduction in the number of neutrophils in the BAL fluid. Each value is mean SEM for 11-12 mice.

 

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