Effect of interleukin-10 on newborn piglet brain following hypoxia-ischemia and endotoxin-induced inflammation.
OBJECTIVE
Previous animal studies indicated that interleukin (IL)-10 attenuates the inflammatory response to a challenge by inflammation and hypoxia-ischemia, but the effect of IL-10 administration after onset of inflammation has not been studied. We wanted to assess (1) whether IL-10 had a beneficial effect on brain metabolism and microcirculation in newborn piglets after an inflammatory, hypoxic and ischemic challenge, and (2) whether IL-10 had any harmful effects per se.


METHODS
Anesthetized piglets were randomized to control (n = 8), IL-10 (n = 10), endotoxin (ETX) (n = 10), or ETX and IL-10 (ETX/IL-10) (n = 10) groups. IL-10 was administered after pretreatment with saline in the IL-10 group or ETX in the ETX/IL-10 group. Then, cerebral hypoxia and ischemia was induced by bilateral clamping of the common carotid arteries and ventilation with 8% O(2) for 30 min, followed by 4 h of reoxygenation and reperfusion. Extracellular levels of lactate, pyruvate, and glycerol were measured with microdialysis in periventricular white matter and parasagittal subcortical tissue, and tissue oxygenation and microcirculation were measured with Doppler technique. We compared the areas under the concentration-time and flow-time curves and maximum concentrations between (1) the ETX/IL-10 and ETX groups, and (2) the control and IL-10 groups.


RESULTS
We found no differences between (1) the ETX/IL-10 and ETX groups, and also no differences between (2) the control and IL-10 groups.


CONCLUSIONS
We could not show that the treatment with IL-10 after onset of inflammation had neuroprotective effects in the newborn piglet brain. IL-10 did not attenuate metabolism in the absence of ETX-induced inflammation.
Lyng
Kristin
K
Department of Pediatric Research, University of Oslo, Oslo, Norway. kristin.lyng@klinmed.uio.no
Munkeby
Berit H
BH
Saugstad
Ola Didrik
OD
Stray-Pedersen
Babill
B
Frøen
J Frederik
JF
D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004660:Encephalitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D004731:Endotoxins; D005990:Glycerol / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000378:metabolism*; D016753:Interleukin-10 / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008833:Microcirculation / Q000187:drug effects; D017551:Microdialysis; D009994:Osmolar Concentration; D010101:Oxygen Consumption / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019344:Lactic Acid; D019289:Pyruvic Acid; D005990:Glycerol