Interleukin-1 Expression During Hyperoxic Lung Injury in the Mouse

An important component of the pathophysiologic response to hyperoxia (O2) is pulmonary inflammation, although the roles of specific inflammatory mediators during pulmonary O2 toxicity are not completely known. Interleukin-1 (IL-1) is an early inflammatory mediator and is sufficient to elicit many of the responses associated with acute injury. The IL-1 family comprises two bioactive proteins, IL-1α and IL-1β, and their natural antagonist IL-1ra. Here we report studies of IL-1 regulation during hyperoxic lung injury in the adult mouse. When assayed by Northern blot, increases in IL-1β mRNA were seen after 2 days of hyperoxia. In contrast, IL-1α mRNA was barely detectable before 4 days of hyperoxia. To further understand the cellular origin of IL-1β expression in lungs, in situ hybridization and immunohistochemical analyses were performed. IL-1β mRNA or protein was not detected in the lungs of unexposed animals. At 3 days, we observed the accumulation of IL-1β transcripts in pulmonary interstitial macrophages and in a subset of neutrophils, and immunodetectable IL-1β protein was co-localized in adjacent sections. At 4 days of exposure, IL-1β transcripts were widespread in lung tissue, but many areas rich in IL-1β mRNA were devoid of immunodetectable IL-1β. However, it is not known whether increased synthesis of IL-1β or the uncoupling of IL-1β protein and mRNA accumulation has a role in pathophysiology of pulmonary O2 toxicity.