Kaneta Takehiro, Kusnecov Alexander W
Department of Psychology, Biopsychology and Behavioral Neuroscience Program, Rutgers University, 152 Frelinghuysen Road, Piscataway, NJ 08855, USA.
Brain Behav Immun. 2005 Mar;19(2):138-46. doi: 10.1016/j.bbi.2004.06.002.
Bacterial superantigens, such as the staphylococcal enterotoxins, exert a strong capacity for in vivo stimulation of T cell proliferation and cytokine production. Previously, staphylococcal enterotoxin A (SEA) was shown to induce an anorexic effect under novel contextual conditions of testing, and produced an increase in plasma ACTH and corticosterone levels in C57BL/6J mice. In the present study, the role of corticotropin releasing hormone (CRH) in promoting these effects of SEA was addressed via intracerebroventricular (icv) administration of alpha-helical CRH(9-41) ((alpha)hCRH), a non-selective CRH receptor antagonist, and astressin-2B, a selective CRH receptor 2 antagonist. The efficacy of (alpha)hCRH and astressin-2B in blocking anorexic responses to CRH and urocortin under the current conditions of testing was first confirmed. Subsequently, it was found that (alpha)hCRH (20 microg icv), but not astressin-2B (10 and 25 microg icv), significantly attenuated the anorexia induced by SEA. This suggested that central CRH is involved in mediating the anorexia induced by SEA, but potentially through CRH receptor 1. Additional results revealed that plasma ACTH stimulation in response to SEA was not significantly attenuated by either antagonist administered icv. However, the plasma corticosterone elevation showed a modest, but significant, attenuation in SEA challenged mice given (alpha)hCRH. These data suggest a possible influence of central CRH on adrenocorticoid activity subsequent to SEA challenge. More importantly, it appears that central activation of CRH receptors is a consequence of SEA challenge, and this likely contributes to its anorexic effects.
细菌超抗原，如葡萄球菌肠毒素，具有在体内强烈刺激T细胞增殖和细胞因子产生的能力。此前研究表明，在新的测试环境条件下，葡萄球菌肠毒素A（SEA）可诱导厌食效应，并使C57BL/6J小鼠血浆促肾上腺皮质激素（ACTH）和皮质酮水平升高。在本研究中，通过脑室内（icv）注射α-螺旋促肾上腺皮质激素释放激素（CRH）（9-41）（αhCRH）（一种非选择性CRH受体拮抗剂）和astressin-2B（一种选择性CRH受体2拮抗剂），探讨了促肾上腺皮质激素释放激素（CRH）在促进SEA这些效应中的作用。首先证实了αhCRH和astressin-2B在当前测试条件下阻断对CRH和尿皮质素厌食反应的功效。随后发现，αhCRH（20微克icv）而非astressin-2B（10和25微克icv）能显著减轻SEA诱导的厌食。这表明中枢CRH参与介导SEA诱导的厌食，但可能是通过CRH受体1。其他结果显示，icv注射的任何一种拮抗剂均未显著减弱SEA刺激引起的血浆ACTH升高。然而，给予αhCRH的SEA攻击小鼠血浆皮质酮升高有适度但显著的减弱。这些数据表明中枢CRH对SEA攻击后肾上腺皮质活动可能有影响。更重要地是，似乎CRH受体的中枢激活是SEA攻击的结果，这可能导致其厌食效应。
