Intratracheal injection of endotoxin and cytokines: II. Interleukin-6 and transforming growth factor beta inhibit acute inflammation

Thomas R. Ulich, Songmei Yin, Kaizhi Guo, Eunhee S. Yi, Daniel Remick, Juan Del Castillo

Research output: Contribution to journalArticlepeer-review

215 Scopus citations


The nature of the endogenous mediators that downregulate and curtail the exodus of neutrophils into local acute inflammatory sites is unknown. In the present report, interleukin-6 (IL-6) and transforming growth factor beta (TGFβ), members of a family of macrophage-derived proteins known as cytokines, are shown to inhibit significantly the acute neutrophilic exodus caused by an intratracheal injection of endotoxin (LPS), a proinflammatory component of the cell walls of gram-negative bacteria. Transforming growth factor beta (10 μg) and IL-6 (10 μg) coinjected intratracheally with LPS (10 μg) each inhibited the number of neutrophils in 6-hour bronchoalveolar lavage (BAL) specimens by approximately 50%. The intratracheal coinjection of IL-6, TGFβ, and LPS inhibited the LPS-induced neutrophilic inflammatory exodus by nearly 75%. Interleukin-6 also is shown to be endogenously upregulated within the lung after intratracheal challenge with endotoxin, providing evidence that IL-6 may represent an endogenous negative feedback mechanism to inhibit endotoxin-initiated cytokine-mediated acute inflammation. Interleukin-6 and TGFβ both strongly inhibited the quantity of TNF-α recovered in the BAL fluid of LPS-challenged rats, suggesting that downregulation of LPS-induced TNF-α production within the lung represents one mechanism whereby IL-6 and TGFβ exert an antiinflammatory action. Interleukin-6 and TGFβ represent novel pharmacologic and, probably, endogenous inhibitors of acute inflammation.

Original languageEnglish (US)
Pages (from-to)1097-1101
Number of pages5
JournalAmerican Journal of Pathology
Issue number5
StatePublished - May 1991

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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