Regulatory effects of interleukin-10 on lung ischemia-reperfusion injury.
OBJECTIVE
Interleukin-10, a cytokine with antiinflammatory activities, was studied to determine its effects on development of early lung reperfusion injury.


METHODS
Adult male rats underwent 90 minutes of left lung ischemia followed by 4 hours of reperfusion. Time-matched sham-operated control rats underwent hilar dissection but not lung ischemia. Lung injury was measured by vascular permeability to bovine serum albumin tagged with iodine 125. To evaluate the effect of exogenous interleukin-10, additional animals received interleukin-10 intravenously before ischemia. To assess the role of endogenous interleukin-10, animals received rabbit antimouse interleukin-10 immunoglobin G (or preimmune rabbit immunoglobin G) before ischemia.


RESULTS
Compared with sham control rats, ischemia-reperfusion control rats demonstrated significantly more lung injury. Animals receiving interleukin-10 had significantly less lung injury than did ischemia-reperfusion control rats. Animals receiving antiinterleukin-10 had significantly more lung injury than did animals receiving preimmune immunoglobin G. Alveolar macrophages from animals after 90 minutes of lung ischemia produced more tumor necrosis factor-alpha in culture than did unstimulated macrophages; this production was reduced significantly by the addition of interleukin-10 to the culture medium.


CONCLUSIONS
Endogenous interleukin-10 has a protective effect against early lung reperfusion injury, and interleukin-10 administration can reduce lung reperfusion injury, perhaps in part through its ability to reduce production by alveolar macrophages of tumor necrosis factor-alpha, a known proinflammatory cytokine.
Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor 48109, USA.
M J
MJ
Eppinger
P A
PA
Ward
S F
SF
Bolling
G M
GM
Deeb
D000818:Animals; D002199:Capillary Permeability; D007074:Immunoglobulin G / Q000627:therapeutic use; D016753:Interleukin-10 / Q000502:physiology*; D007511:Ischemia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10