Inflammatory Cytokines and Lung Toxicity

Exposure to airborne particles and gases including silica, asbestos, diesel exhaust, and ozone is associated with significant risk of pulmonary and cardiovascular morbidity and mortality. Increasing evidence suggests that macrophages and inflammatory mediators released, including cytokines, play a role in the pathogenic process. In response to lung injury, alveolar macrophages become activated and release increased quantities of cytokines such as TNF-α, IL-1, IL-6, and IL-10, as well as chemokines and growth factors such as TGF-β and PDGF. Although these mediators are released to protect the host and initiate wound repair, when generated in excessive amounts or at inappropriate times or places, they can damage host tissue and exacerbate or perpetuate injury. In this chapter, the role of inflammatory cytokines and growth factors released by macrophages in xenobiotic-induced pulmonary toxicity is reviewed. Potential mechanisms mediating expression of cytokine genes and the implications to human health are also discussed.