An age‐associated increase in pulmonary inflammation after burn injury is abrogated by CXCR2 inhibition

Burn patients over the age of 60 are at a greater risk for developing pulmonary complica- tions than younger patients. The mechanisms for this, however, have yet to be elucidated. The ob- jective of this study was to determine whether in- creased chemoattraction plays a role in the age- related differences in pulmonary inflammation af- ter burn injury. At 6 or 24 h after receiving sham or 15% total body surface area scald injury, lungs from young and aged mice were analyzed for leu- kocyte content by histological examination and im- munostaining. Lungs were then homogenized, and levels of neutrophil chemokines, MIP-2 and KC, were measured. At 6 h after burn, the number of neutrophils was four times higher in the lungs of both burn groups compared with aged-matched controls (P<0.05), but no age difference was evi- dent. At 24 h, in contrast, neutrophils returned to sham levels in the lungs of young, burn-injured mice (P<0.05) but did not change in the lungs of aged, burn-injured mice. Pulmonary levels of the neutrophil chemokine KC but not MIP-2 were con- sistently three times higher in aged, burn-injured mice compared with young, burn-injured mice at both time-points analyzed. Administration with anti-CXCR2 antibody completely abrogated the ex- cessive pulmonary neutrophil content by 24 h (P<0.05), while not affecting the inflammatory re- sponse of the wounds. These studies show that CXCR2-mediated chemoattraction is involved in the pulmonary inflammatory response after burn and suggest that aged individuals sustaining a burn injury may benefit from treatment strategies that target neutrophil chemokines. J. Leukoc. Biol. 83: 1493-1501; 2008.