Innate immune responses and chronic obstructive pulmonary disease: "Terminator" or "Terminator 2"?

Abstract

Innate immune responses appear to be partially responsible for maintaining inflammation and tissue destruction in chronic obstructive pulmonary disease. In the early stages of the disease in smokers, the airways are bombarded with large quantities of particulate material, and activation of phagocytic cells results in the release of many of the mediators believed to remodel the airways. Ironically, failure of the innate immune defense system, either by inherited deficiency or as a result of chronic smoke inhalation, is likely to result in increased susceptibility to infectious disease and exacerbations of chronic obstructive pulmonary disease. It is well known that deficiencies in the production of collectins, pentraxins, and complement can lead to increased infections, and several studies indicate that deficiency in one or another innate defense component is associated with increased exacerbations. Corticosteroids reduce exacerbations in part because of their ability to boost the production of innate host-defense molecules. Therapeutic approaches that stimulate the generation of antimicrobial molecules in the lungs might be able to reduce disease exacerbations.

Figure 1.

Systemic inflammation and local host defense in the lungs. A complex relationship exists between local host-defense responses, systemic host-defense responses (including elevation of circulating acute phase proteins), local inflammation, and systemic inflammation (mediated in part by elevated levels of inflammatory cytokines in the circulation). Corticosteroids (GC) are generally effective antiinflammatory drugs but have the characteristic that they enhance some innate host defenses (e.g., systemic expression of acute phase proteins and expression of several classes of innate immune effecter molecules locally). Because GC can suppress the release of cytokines that stimulate the acute phase response (interleukin [IL]-1, tumor necrosis α [TNF-α], IL-6), they often reduce levels of acute phase proteins despite having a stimulatory effect on hepatic production. CRP = C-reactive protein; SAP = serum amyloid P; C′ = complement.