Mycobacterial lipoarabinomannan induces an inflammatory response in the mouse lung. A role for interleukin-1.

Abstract

Lipoarabinomannan (LAM), a cell wall component of Mycobacterium tuberculosis, induces the production of cytokines and chemokines in vitro. Interleukin-1 (IL-1) contributes to granuloma formation in tuberculosis (TB), and exerts effects via the IL-1 receptor type I (IL-1R). To determine the effects of LAM in the pulmonary compartment in vivo and to establish the role of endogenous IL-1 herein, normal and IL-1R deficient ((-/-)) mice were intranasally inoculated with LAM (50 microgram). In normal mice, LAM resulted in a neutrophilic cell influx into the bronchoalveolar lavage fluid (BALF). LAM also induced increases in the lung concentrations of macrophage inflammatory protein-2 (MIP-2), keratinocyte (KC), tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, and IL-1beta. IL-1R(-/-) mice had less influx of granulocytes in their BALF than wild-type mice. Also, lung TNF-alpha levels were lower in IL-1R(-/-) mice. LAM may be an important stimulator of innate immunity in infection with M. tuberculosis via mechanisms that involve endogenous IL-1 activity.