Otterness I G, Seymour P A, Golden H W, Reynolds J A, Daumy G O
Department of Immunology, Drug Safety Evaluation and Molecular Genetics, Central Research Division, Pfizer, Inc., Groton, CT 06340.
Physiol Behav. 1988;43(6):797-804. doi: 10.1016/0031-9384(88)90379-4.
Recombinant murine IL-1 alpha was administered continuously to rats by means of osmotic pumps implanted intraperitoneally. Continuous infusion of rIL-1 alpha in a range between 0.12 and 12.0 micrograms/day for four days was found to produce concentration-dependent weight loss. Behavioral parameters were continuously monitored and recorded at the 3.0 micrograms/day concentration in electronically-monitored activity cages during Days 2 through 5 of rIL-1 alpha administration. Parameters were separated into those affected during the dark phase (active period) or the light phase (resting period). Eating activity was found to be significantly reduced during each dark period through day 5, when compared with either untreated or PBS vehicle-infused animals. During the fourth and fifth days of infusion, however, eating behavior in animals infused with rIL-1 alpha began to increase toward control level in the latter, but not the earlier, half of the dark period. In contrast, drinking behavior was found to be significantly elevated only during the light periods. Continuous infusion of rIL-1 alpha also produced significant reductions in both horizontal locomotor activity (crossovers) and vertical locomotor activity (rears). However, in contrast to the trend toward a return of normal eating behavior, locomotor activity remained decreased through the fifth day of rIL-1 alpha infusion. These results suggest changes that could be produced by IL-1 in chronic inflammatory disease and infection.
通过腹腔内植入渗透泵，将重组小鼠白细胞介素-1α持续给予大鼠。连续4天以每天0.12至12.0微克的剂量持续输注重组白细胞介素-1α，结果发现会产生浓度依赖性体重减轻。在给予重组白细胞介素-1α的第2天至第5天期间，在电子监测的活动笼中，以每天3.0微克的浓度持续监测并记录行为参数。这些参数被分为在黑暗期（活跃期）或光照期（休息期）受到影响的参数。与未治疗或输注磷酸盐缓冲盐水的动物相比，在第5天之前的每个黑暗期，进食活动均显著减少。然而，在输注的第4天和第5天，在黑暗期的后半段而非前半段，接受重组白细胞介素-1α输注的动物的进食行为开始朝着对照水平增加。相比之下，仅在光照期发现饮水行为显著增加。连续输注重组白细胞介素-1α还导致水平运动活动（穿越次数）和垂直运动活动（站立次数）均显著减少。然而，与进食行为恢复正常的趋势相反，在重组白细胞介素-1α输注的第5天之前，运动活动一直保持下降。这些结果提示白细胞介素-1在慢性炎症性疾病和感染中可能产生的变化。
