Opioids and clonidine modulate cytokine production and opioid receptor expression in neonatal immune cells.
Opioids and clonidine modulate cytokine production and opioid receptor expression in neonatal immune cells.
复制标题
DOI：
10.1038/jp.2012.124
复制
发表时间：
2013-05
影响因子：
2.9
通讯作者：
Gauda, E. B.
中科院分区：
文献类型：
--
作者：
Chavez-Valdez, R.;Kovell, L.;Ahlawat, R.;McLemore, G. L.;Wills-Karp, M.;Gauda, E. B.
阿片类药物和可乐定可直接或间接激活免疫细胞上表达的阿片受体，用于新生儿的镇静、镇痛和控制阿片戒断。因此，我们的目的是研究不同阿片类药物和可乐定的临床相关浓度如何改变早产儿和足月儿培养全血中的细胞因子水平。使用早产儿的血液（胎龄≤ 30周，n=7）和足月（≥37周GA，n=19）婴儿，我们研究了细胞因子谱的变化（IL-1β、IL-6、IL-8、IL-10、IL-12 p70和TNF-α）、环磷酸腺苷（cAMP）水平和μ-、δ-、和κ-阿片受体（OPR）基因和蛋白表达。在体外暴露于浓度范围从0到1 mM的吗啡、美沙酮、芬太尼或可乐定后，在足月儿的培养血液中，IL-10水平是早产儿的146倍。吗啡和美沙酮，而不是芬太尼，在>10- 5 M，降低所有测试的细胞因子，除了IL-8。相反，可乐定在<10- 9 M时增加IL-6，而在>10- 5 M时增加IL-1β和降低TNF-α水平。所有细胞因子的变化遵循相同的模式，在早产儿和足月婴儿培养的血液和匹配的cAMP水平的增加。所有三种μ-、δ-和κ-OPR基因在来自早产儿和足月婴儿的单核细胞中表达。吗啡、美沙酮和可乐定在>10- 5 M时可降低μ-OPR的表达，但不影响δ-或κ-OPR的表达。在暴露于临床相关浓度的吗啡和美沙酮的新生儿单核细胞中观察到的普遍细胞因子抑制沿着μ-OPR表达下调，与芬太尼和可乐定观察到的适度效应形成对比。因此，我们推测芬太尼和可乐定可能是更安全的治疗选择，用于镇静和控制阿片类药物戒断和疼痛的新生儿。
Opioids and clonidine, used in for sedation, analgesia and control of opioid withdrawal in neonates, directly or indirectly activate opioid receptors expressed in immune cells. Therefore, our objective is to study how clinically relevant concentrations of different opioids and clonidine change cytokine levels in cultured whole blood from preterm and full-term infants. Using blood from preterm (≤ 30 weeks gestational age, n=7) and full-term (≥37 weeks GA, n=19) infants, we investigated the changes in cytokine profile (IL-1β, IL-6, IL-8, IL-10, IL-12p70, and TNF-α), cyclic adenosine monophosphate (cAMP) levels and μ-, δ-, and κ- opioid receptor (OPR) gene and protein expression following in-vitro exposure to morphine, methadone, fentanyl, or clonidine at increasing concentrations ranging from 0 to 1 mM. Following LPS activation, IL-10 levels were 146-fold greater in cultured blood from full-term than from preterm infants. Morphine and methadone, but not fentanyl, at >10-5M decreased all tested cytokines except IL-8. In contrast, clonidine at <10-9M increased IL-6, while at >10-5M increased IL-1β and decreased TNF-α levels. All cytokine changes followed the same patterns in preterm and full-term infant cultured blood and matched increases in cAMP levels. All three μ-, δ- and κ-OPR genes were expressed in mononuclear cells from preterm and full-term infants. Morphine, methadone and clonidine, but not fentanyl, at >10-5M decreased the expression of μ-OPR, but not δ- or κ-OPRs. Generalized cytokine suppression along with downregulation of μ-OPR expression observed in neonatal mononuclear cells exposed to morphine and methadone at clinically relevant concentrations contrast with the modest effects observed with fentanyl and clonidine. Therefore, we speculate that fentanyl and clonidine may be safer therapeutic choices for sedation and control of opioid withdrawal and pain in neonates.
登录
查看更多内容
影响因子：
4.2
作者：
Felder, C;Uehlinger, C;Eap, CB
通讯作者：
Eap, CB
影响因子：
4.7
作者：
Gyires, K;Rónai, AZ;Fürst, S
通讯作者：
Fürst, S
DOI：
10.1053/j.jvca.2005.03.008
发表时间：
2005-06-01
影响因子：
2.8
作者：
Kussman, BD;Zurakowski, D;Laussen, PC
通讯作者：
Laussen, PC
影响因子：
9.8
作者：
Bouwmeester, NJ;Anderson, BJ;Holford, NHG
通讯作者：
Holford, NHG
影响因子：
2.9
作者：
Kaneider, NC;Dunzendorfer, S;Wiedermann, CJ
通讯作者：
Wiedermann, CJ