McLaughlin C L, Rogan G J, Tou J, Baile C A, Joy W D
Animal Science Division, Monsanto Company, St. Louis, MO 63198.
Physiol Behav. 1992 Dec;52(6):1155-60. doi: 10.1016/0031-9384(92)90475-h.
Food intake and body temperature are two of many factors affected by IL-1 beta, a cytokine which is produced in response to tissue injury and inflammatory processes. In the present experiment, a tripeptide IL-1 beta antagonist which blocked IL-1 beta-induced hyperalgesia was tested for the ability to block IL-1 beta-induced effects on food intake and body temperature. Food intake was decreased 4-22 h after intraperitoneal (IP) administration of 1.25, 1.88, or 2.50 micrograms IL-1 beta/rat, and 0-22 h food intake was decreased by 1.88 and 2.50 micrograms IL-1 beta/rat. The effect of 1.25 micrograms IL-1 beta/rat on food intake measured 4 and 22 h after (IP) injection was blocked by coadministration of 5 mg tripeptide IL-1 beta antagonist. However, 25 mg tripeptide IL-1 beta antagonist/rat plus 1.25 micrograms IL-1 beta/rat decreased 0-22 h food intake more than IL-1 beta alone. Administration (IP) of 1.25 micrograms IL-1 beta/rat increased body temperature 1 degrees C 4 h later, and 5 and 25 mg tripeptide IL-1 beta antagonist/rat blocked this increase. Although food intake remained decreased after IL-1 beta administration alone or with 25 mg tripeptide IL-1 beta antagonist/rat for 22 h, body temperature returned to normal under these conditions. Thus, a tripeptide IL-1 beta antagonist shown to block IL-1 beta-induced hyperalgesia also blocked food intake and body temperature responses to IL-1 beta, although the effective doses of IL-1 beta and the tripeptide IL-1 beta antagonist differ by 4,000-fold when both are administered peripherally.
食物摄入量和体温是受白细胞介素-1β(IL-1β)影响的众多因素中的两个,IL-1β是一种在组织损伤和炎症过程中产生的细胞因子。在本实验中,测试了一种能阻断IL-1β诱导的痛觉过敏的三肽IL-1β拮抗剂对阻断IL-1β诱导的食物摄入量和体温影响的能力。腹腔注射(IP)1.25、1.88或2.50微克IL-1β/大鼠后4至22小时食物摄入量减少,而0至22小时食物摄入量在注射1.88和2.50微克IL-1β/大鼠时减少。腹腔注射(IP)1.25微克IL-1β/大鼠后4小时和22小时测量的食物摄入量效应,在同时给予5毫克三肽IL-1β拮抗剂时被阻断。然而,25毫克三肽IL-1β拮抗剂/大鼠加1.25微克IL-1β/大鼠使0至22小时食物摄入量的减少比单独使用IL-1β时更大。腹腔注射(IP)1.25微克IL-1β/大鼠4小时后体温升高1摄氏度,而5毫克和25毫克三肽IL-1β拮抗剂/大鼠可阻断这种升高。尽管单独给予IL-1β或与25毫克三肽IL-1β拮抗剂/大鼠一起给药22小时后食物摄入量仍保持减少,但在这些条件下体温恢复正常。因此,一种已证明能阻断IL-1β诱导的痛觉过敏的三肽IL-1β拮抗剂也阻断了对IL-1β的食物摄入量和体温反应,尽管当两者都经外周给药时,IL-1β和三肽IL-1β拮抗剂的有效剂量相差4000倍。