Johnson Paulette M, Vogt Sherri K, Burney Mary W, Muglia Louis J
Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri 63110, USA.
Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E650-6. doi: 10.1152/ajpendo.00388.2001.
Anorexia and weight loss are frequent complications of acute and chronic infections and result from induction of cytokines, prostaglandins, and other inflammatory mediators that are critical for pathogen elimination. Selective attenuation of the hypophagic response to infection and maintenance of the production of factors essential for infection control would be a useful addition to antimicrobial therapy in the treatment of human disease. Here, we evaluate the relative contribution of cyclooxygenase (COX)-1- and COX-2-derived prostaglandins to anorexia and weight loss precipitated by systemic immune activation by lipopolysaccharide (LPS). Using COX isoform-selective pharmacological inhibitors and gene knockout mice, we found that COX-2 inhibition during LPS-induced inflammation results in preserved food intake and maintenance of body weight, whereas COX-1 inhibition results in augmented and prolonged weight loss. Regulation of neuropeptide Y, corticotropin-releasing hormone, leptin, and interleukin-6 does not change as a function of COX-2 inhibition after LPS administration. Our data implicate COX-2 inhibition as a therapeutic target to maintain nutritional status while still allowing a normal cytokine response during infection.
厌食和体重减轻是急慢性感染常见的并发症，由细胞因子、前列腺素和其他对病原体清除至关重要的炎症介质诱导产生。选择性减弱对感染的摄食减少反应并维持感染控制所需因子的产生，将是人类疾病治疗中抗菌治疗的有益补充。在此，我们评估环氧化酶（COX）-1和COX-2衍生的前列腺素对脂多糖（LPS）引起的全身免疫激活所致厌食和体重减轻的相对贡献。使用COX同工型选择性药理抑制剂和基因敲除小鼠，我们发现LPS诱导炎症期间抑制COX-2可使食物摄入量保持不变并维持体重，而抑制COX-1则导致体重减轻加剧且持续时间延长。给予LPS后，神经肽Y、促肾上腺皮质激素释放激素、瘦素和白细胞介素-6的调节不会因COX-2抑制而改变。我们的数据表明，抑制COX-2作为一种治疗靶点，可在感染期间维持营养状况，同时仍允许正常的细胞因子反应。
