Chemokines in acute lung injury

Ward PA. Role of complement, chemokines and regulatory cytokines in acute lung injury. Ann NY Acad Sci 1996 796 104-112. 

Table 2 shows the studies of a-chemokines and p-chemokines in lung fluids of patients with ARDS. These studies in humans are supported by a number of studies in experimental animals showing that inhibition of a- and p-chemokine function modulates the severity of acute lung injury in experimental systems. 

The role of GSH in detoxification of HD has been somewhat controversial. Sciuto et al. (2007) have shown that there may be a biphasic response to HD intoxication. Testing for pulmonary toxicity using an intravascular HD injection model in rats, it was shown that at Ih post-exposure, BAL revealed a dose-dependent inflammatory stage that decreased over time from 3 to 24 h. Macrophage inflammatory protein (MIP-2) was the predominant chemokine in the BAL followed by ILlp, ILIO, and TNFa. A second phase involved changes in the antioxidant response pathway, which was mostly affected at 6h post-challenge. HD exposure increased BALF protein, GSH, and the activities of GSH peroxidase (GPX), catalase, GSH reductase, and SOD (Sciuto et al., 2007). Laskin et al. (2010) summarized that in some animal models of acute lung injury with HD and HD-like compounds, antioxidant markers such as GPX and GSH... 

A second study examined a model of systemic inflammatory response syndrome (SIRS) with lung injury secondary to acute caerulin-induced pancreatitis. Whereas the initial pancreatic injury was not blunted, the lung injury was diminished in CCR-1 (-/-) mice. Thus, both of these studies indicated that in the mouse, CCRl is an important PMN neutrophil agonist, and cautioned against extrapolating between species concerning chemokine function. 

This chapter reviews information that links chemokines and inflammatory responses in the lungs of humans with ARDS. This information provides the background for studies in animal models concerning the role of individual pathways in the acute inflammatory responses in the lungs. Information from human studies is descriptive at best, but offers a framework for the formation of specific testable hypotheses about pathogenesis of lung injury that can be investigated in animal model systems. 

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