TY - JOUR
T1 - Intratracheal injection of endotoxin and cytokines
T2 - II. Interleukin-6 and transforming growth factor beta inhibit acute inflammation
AU - Ulich, Thomas R.
AU - Yin, Songmei
AU - Guo, Kaizhi
AU - Yi, Eunhee S.
AU - Remick, Daniel
AU - Del Castillo, Juan
PY - 1991/5
Y1 - 1991/5
N2 - 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.
AB - 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.
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M3 - Article
C2 - 2024703
AN - SCOPUS:0025805971
SN - 0002-9440
VL - 138
SP - 1097
EP - 1101
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -