Effect of Interleukin-10 on Newborn Piglet Brain following Hypoxia-Ischemia and Endotoxin-Induced Inflammation

Abstract

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% O₂ 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. Conclusion: 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.

IL-1 Receptor Antagonist Protects against Placental and Neurodevelopmental Defects Induced by Maternal Inflammation

“…Unfortunately, additional trials and meta-analysis showed that pre-or postnatal corticosteroids eventually do not provide neurobehavioral benefit and could result in adverse effects in certain therapeutic designs (54). Conflicting results and fetal adverse effects such as ductal constriction have been reported in neonates treated prenatally with nonsteroidal anti-inflammatory drugs (55)(56)(57), emphasizing the need to better restrict the target of blocking agents to optimally balance beneficial and adverse effects. Maternal IL-1Ra therapy, as we tested, at doses already recommended for human inflammatory diseases (58) may meet this safety/efficacy criterion.…”

Involvement of Pro- and Anti-Inflammatory Cytokines and Chemokines in the Pathophysiology of Traumatic Brain Injury

“…Nonetheless, no protection was seen after IL-10 administration in piglets subjected to hypoxicischemic insult. 46 In humans, high levels of IL-10 have been measured in the CSF of children with brain injury; surprisingly, this increase has been correlated with adverse outcome. 47 Increased production of IL-10 in human CSF of adult TBI patients corresponded to decreases in tumor necrosis factor levels; however, no correlation was found between IL-10 and outcome.…”

Cytokines and Myelination in the Central Nervous System

“…As an immunomodulator, IL-10 inhibits Th1 proliferation and effector cytokine production. A neuroprotective effect of IL-10 has been documented in rats receiving IL-10 either intracranially or into the peritoneum during brain injury[31]. …”

“…An anti-inflammatory mechanism seems likely to be involved in protection by this “preconditioning” because it reduced proinflammatory markers such as nuclear factor kappa B (NFκB) and microglial activation[173]. Neuroprotection by anti-inflammatory treatment has also been observed using neutralizing IL-1 antibody[174] and IL-10[31]. Administration of exogenous erythropoietin (EPO) starting 24 h after hypoxia/ischemia also has been shown to be neuroprotective in neonatal rats by preventing the rise in IL-1β and attenuating infiltration of leukocytes into the hypoxic/ischemic brain region[175].…”