Szabo G, Kodys K, Miller-Graziano C L
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
J Clin Immunol. 1991 Nov;11(6):336-44. doi: 10.1007/BF00918799.
Aberrant monocyte mediator production is pivotal in the development of posttrauma immunosuppression. We have previously shown that immunodepressed trauma patients' monocytes produce elevated interleukin-6, suggesting their in vivo preactivation. This study confirms that preactivated patients' Mø produce greater levels of IL-6 than normals' Mø to the same in the in vitro Fc gamma RI stimulation. We also demonstrate the capacity of interleukin-4 to downregulate the elevated interleukin-6 production of trauma patients' in vivo preactivated monocytes. Monocyte interleukin-6 downregulation by interleukin-4 is dose dependent and occurs whether Fc gamma RI cross-linking, muramyl dipeptide, indomethacin plus muramyl dipeptide, or interferon-gamma plus muramyl dipeptide is the interleukin-6 inducing stimulus. Furthermore, interleukin-4-dependent downregulation of monocyte interleukin-6 expression is confirmed at both the supernatant and the mRNA levels. Simultaneous downregulation of posttrauma elevated monokines implies a possible therapeutic benefit of interleukin-4 for trauma patients.
异常单核细胞介质产生在创伤后免疫抑制的发展中起关键作用。我们之前已经表明，免疫抑制的创伤患者单核细胞产生升高的白细胞介素-6，提示其体内预激活。本研究证实，在体外FcγRI刺激下，预激活患者的单核细胞比正常人的单核细胞产生更高水平的IL-6。我们还证明了白细胞介素-4下调创伤患者体内预激活单核细胞升高的白细胞介素-6产生的能力。白细胞介素-4对单核细胞白细胞介素-6的下调是剂量依赖性的，并且无论FcγRI交联、胞壁酰二肽、吲哚美辛加胞壁酰二肽或干扰素-γ加胞壁酰二肽作为白细胞介素-6诱导刺激物都会发生。此外，在超上清液和mRNA水平均证实了白细胞介素-4依赖性单核细胞白细胞介素-6表达下调。创伤后升高的单核因子的同时下调意味着白细胞介素-4对创伤患者可能具有治疗益处。
