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 language||English (US)|
|Number of pages||5|
|Journal||American Journal of Pathology|
|State||Published - Jan 1 1991|
ASJC Scopus subject areas
- Pathology and Forensic Medicine