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John D. Meyer, MD; Roger W. Yurt, MD; Roderick Duhaney, MS; David G. Hesse, MD; Kevin J. Tracey, MD; Yuman Fong, MD; Madhu Verma, MA; G. Tom Shires, MD; Peter Dineen, MD; Stephen F. Lowry, MD; John Mihran Davis, MD

Arch Surg. 1988;123(12):1454-1458.

Abstract
• In an in vivo study of five normal volunteers infused with endotoxin (20 U/kg of US reference endotoxin lot EC-5), increased neutrophil (PMN) generation of leukotriene B₄ and chemotaxis to leukotriene B₄ were found concomitantly with elevated plasma tumor necrosis factor (TNF) levels. To clarify the role of TNF in PMN activation, neutrophil responsiveness after in vitro treatment with TNF was examined. Neutrophils from seven normal subjects were incubated with TNF for 30 minutes and tested for chemotaxis to leukotriene B₄, formyl-methionyl-leucyl-phenylalanine and zymosan-activated serum, or the calcium ionophore A23187 to assess leukotriene B₄ generation. A range of 10^–13 to 10^–9 mol/L of TNF was used for these assays. When 10^–9 mol/L of TNF was used, the amount of leukotriene B₄ that was produced was significantly greater than in control cells. The effect of TNF on PMN chemotaxis was uniformly inhibitory for the three stimuli at 10^–10 mol/L compared with untreated cells. At a picomolar range, PMN migration to leukotriene B₄, but not to zymosan-activated serum or formyl-methionyl-leucyl-phenylalanine, was significantly increased over that of PMNs not exposed to TNF. This suggests that TNF has a specific facilitatory effect on PMN responsiveness for both leukotriene B₄ production and chemotaxis to leukotriene B4 and may be the same signal for this phenomenon in endotoxemic patients.

(Arch Surg 1988;123:1454-1458)

Author Affiliations
From the Department of Surgery, Cornell University Medical College, New York. Dr Meyer is now with the Beth Israel Hospital, Boston.

Footnotes
Accepted for publication Sept 14, 1988.

Read before the Eighth Annual Meeting of the Surgical Infection Society, San Francisco, May 5, 1988.

Reprint requests to 1300 York Ave, New York, NY 10021 (Dr Davis).

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