IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses.
Our studies reveal that endogenous IL-6 plays a crucial antiinflammatory role in both local and systemic acute inflammatory responses by controlling the level of proinflammatory, but not antiinflammatory, cytokines, and that these antiinflammatory activities by IL-6 cannot be compensated for by IL-10 or other IL-6 family members. (J
IL-6 is a pleiotropic cytokine that is commonly produced at local tissue sites and released into circulation in almost all situa-Received for publication 31 July 1997 and accepted in revised form 11 November 1997
To investigate the role of IL-6 in acute lung inflammation, we first examined the content of cytokines including IL-6 and proinflammatory TNF␣ and macrophage inflammatory protein-2 in bronchoalveolar lavage in both IL-6ϩ/ϩ and IL-6Ϫ/Ϫ mice during acute lung inflammation elicited by local lung exposure to LPS aerosol
While LPS induced a TNF␣ response in both IL-6ϩ/ϩ and IL-6Ϫ/Ϫ mice, which reached a maximum level in BAL at 4 h and markedly declined by 24 h, the magnitude of TNF␣ response was more than 100% higher at various time points in IL-6Ϫ/Ϫ mice than in IL-6ϩ/ϩ mice
Similar to IL-10, only small amounts of TGF␤1 were detected in BAL and there was no statistically significant difference found between IL-6ϩ/ϩ and IL-6Ϫ/Ϫ mice
MIP-2 mRNA expression was significantly induced by LPS in both IL-6ϩ/ϩ and IL-6Ϫ/Ϫ mice but was at least 150% stronger in the lung of IL-6Ϫ/Ϫ mice, suggesting that the greater amount of cytokine proteins in the lung of IL-6Ϫ/Ϫ mice was a result of greater mRNA expression
The lack of understanding of other functional aspects of this cytokine in both local and systemic acute inflammatory responses has led to a confounding description about the nature of endogenous IL-6 in literature which has been described as either proinflammatory or antiinflammatory