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Differential Role of Interleukin-6 in Lung Inflammation Induced by Lipoteichoic Acid and Peptidoglycan from Staphylococcus aureus

Laboratory of Experimental Internal Medicine, Division of Clinical Immunology and Rheumatology, Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam; and Eijkman-Winkler Institute, Utrecht University, Utrecht, The Netherlands

Correspondence and requests for reprints should be addressed to Tom van der Poll, Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-130, 1105 AZ Amsterdam, The Netherlands. E-mail: t.vanderpoll{at}AMC.UVA.nl

Lipoteichoic acids (LTA) and peptidoglycans (PepG) are major components of the cell walls of gram-positive bacteria that trigger inflammatory responses in vitro. To study the in vivo effects of LTA and PepG from Staphylococcus aureus in lungs and to determine the role of interleukin (IL)-6 herein, these compounds were intranasally administered to IL-6 gene deficient (IL-6^-/-) and wild type (IL-6^+/+) mice. In IL-6^+/+ mice, LTA and PepG induced acute pulmonary inflammation in a dose-dependent way, characterized by neutrophilic influx and IL-6 production in the bronchoalveolar lavage fluid. Endogenously produced IL-6 attenuated inflammation induced by 10 µg LTA, as reflected by enhanced neutrophil influx, and increased tumor necrosis factor-, macrophage inflammatory protein-1-, and cytokine-induced neutrophil chemoattractant (KC) release into bronchoalveolar lavage fluid of IL-6^-/- mice, compared with IL-6^+/+ mice. By contrast, pulmonary inflammation induced by 100 µg LTA was similar (neutrophil influx) or even tended to be attenuated (cytokine and chemokine release) in IL-6^-/- mice. Endogenous IL-6 increased inflammation induced by PepG, as reflected by decreased neutrophil influx into lungs of IL-6^-/- mice, compared with IL-6^+/+ mice. These data suggest that IL-6 plays an anti-inflammatory role during LTA-induced pulmonary inflammation, which is dependent on the severity of the inflammatory challenge, and a proinflammatory role in peptidoglycan-induced acute lung inflammation. Thus, the contribution of IL-6 to lung inflammation may vary with the stimulus used.

Key Words: interleukin-6 • lipoteichoic acid • peptidoglycan • lung • anti-inflammatory

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