Elevated monocyte interleukin-6 (IL-6) production in immunosppressed trauma patients. II. Downregulation by IL-4.
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.
Szabo
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G
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
Kodys
K
K
Miller-Graziano
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CL
D000328:Adult; D000368:Aged; D002056:Burns / Q000276:immunology / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014947:Wounds and Injuries / Q000276:immunology* / Q000378:metabolism
D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D015232:Dinoprostone