Berg D J, Zhang J, Lauricella D M, Moore S A
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
J Immunol. 2001 Feb 15;166(4):2674-80. doi: 10.4049/jimmunol.166.4.2674.
IL-10 is a potent anti-inflammatory and immune regulatory cytokine. IL-10(-/-) mice produce exaggerated amounts of inflammatory cytokines when stimulated with LPS, indicating that endogenous IL-10 is a central regulator of inflammatory cytokine production in vivo. PGs are lipid mediators that are also produced in large amounts during the inflammatory response. To study the role of IL-10 in the regulation of PG production during the acute inflammatory response, we evaluated LPS-induced cyclooxygenase (COX) expression and PG production in wild-type (wt) and IL-10(-/-) mice. LPS-induced PGE(2) production from IL-10(-/-) spleen cells was 5.6-fold greater than that from wt spleen cells. LPS stimulation resulted in the induction of COX-2 mRNA and protein in both wt and IL-10(-/-) spleen cells; however, the magnitude of increase in COX-2 mRNA was 5.5-fold greater in IL-10(-/-) mice as compared with wt mice. COX-1 protein levels were not affected by LPS stimulation in either wt or IL-10(-/-) mice. Neutralization of IFN-gamma, TNF-alpha, or IL-12 markedly decreased the induction of COX-2 in IL-10(-/-) spleen cells, suggesting that increased inflammatory cytokine production mediates much of the COX-2 induction in IL-10(-/-) mice. Treatment of IL-10(-/-) mice with low doses of LPS resulted in a marked induction of COX-2 mRNA in the spleen, whereas wt mice had minimal expression of COX-2 mRNA. These findings indicate that, in addition to IL-10's central role in the regulation of inflammatory cytokines, endogenous IL-10 is an important regulator of PG production in the response to LPS.
白细胞介素-10是一种强效的抗炎和免疫调节细胞因子。白细胞介素-10基因敲除（IL-10-/-）小鼠在用脂多糖（LPS）刺激时会产生过量的炎性细胞因子，这表明内源性白细胞介素-10是体内炎性细胞因子产生的核心调节因子。前列腺素（PGs）是脂质介质，在炎症反应过程中也大量产生。为了研究白细胞介素-10在急性炎症反应期间对前列腺素产生的调节作用，我们评估了野生型（wt）和白细胞介素-10基因敲除（IL-10-/-）小鼠中LPS诱导的环氧化酶（COX）表达和前列腺素产生情况。LPS诱导IL-10-/-脾细胞产生的前列腺素E2（PGE2）比wt脾细胞高5.6倍。LPS刺激导致wt和IL-10-/-脾细胞中COX-2 mRNA和蛋白的诱导；然而，与wt小鼠相比，IL-10-/-小鼠中COX-2 mRNA的增加幅度高5.5倍。wt或IL-10-/-小鼠中，COX-1蛋白水平均不受LPS刺激的影响。中和γ干扰素（IFN-γ）、肿瘤坏死因子-α（TNF-α）或白细胞介素-12可显著降低IL-10-/-脾细胞中COX-2的诱导，这表明炎性细胞因子产生增加介导了IL-10-/-小鼠中大部分的COX-2诱导。用低剂量LPS处理IL-10-/-小鼠会导致脾脏中COX-2 mRNA的显著诱导，而wt小鼠中COX-2 mRNA的表达极少。这些发现表明，除了白细胞介素-10在炎性细胞因子调节中的核心作用外，内源性白细胞介素-10在对LPS的反应中也是前列腺素产生的重要调节因子。
