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Do Matrix Metalloproteinases Protect or Worsen Pneumonia?

We read with much interest the article by Hartog and colleagues (1) regarding the existence of excessive concentrations of metalloproteinase-8 and -9 without a concomitant increase in the levels of tissue inhibitor of matrix metalloproteinases in the lung of patients with hospital-acquired pneumonia (1). The authors concluded that metalloproteinase-mediated destruction of lung parenchyma might initiate a vicious cycle leading to a perpetuation of the inflammatory response in the lung. Theoretically, a balance in favor of proteases would be associated with increased tissue destruction, disturbance of local blood supply, and, subsequently, further spread of lung infection. However, no evidence was provided in this study to infer whether excessive concentrations of neutrophil-derived metalloproteinases in the bronchoalveolar lavage fluid exerted detrimental effect on the lung. Metalloproteinases may benefit the host because they also have been involved in host defense mechanisms (2); for example, they may promote the secretion of mucus, and hence assist in bacterial clearance and removal of microorganisms from the lung (3). Evaluation of the clinical response to antibiotic therapy in relation to the levels of metalloproteinases may provide an important hint to dissect the beneficial from the detrimental effects of both metalloproteinase-8 and -9 in pneumonia. But this study showed no data regarding whether metalloproteinases levels differed according to clinical response or outcome of the patients after antibiotic therapy. Thus, no conclusion regarding the detrimental or beneficial effect of these proteases in hospital-acquired pneumonia can be drawn from this study.

Esteban C. Gabazza, Osamu Taguchi and Yukihiko Adachi

Mie University School of Medicine Tsu city, Mie prefecture, Japan

FOOTNOTES

Dr. Joerg Braun was given the opportunity to respond to this letter but declined to do so.

REFERENCES

1. Hartog CM, Wermelt JA, Sommerfeld CO, Eichler W, Dalhoff K, Braun J. Pulmonary matrix metalloproteinase excess in hospital-acquired pneumonia. Am J Respir Crit Care Med 2003;167:593–598.[Abstract/Free Full Text]
2. Bottcher T, Spreer A, Azeh I, Nau R, Gerber J. Matrix metalloproteinase-9 deficiency impairs host defense mechanisms against streptococcus pneumoniae in a mouse model of bacterial meningitis. Neurosci Lett 2003;338:201–204.[CrossRef][Medline]
3. Stockley RA. Neutrophils and protease/antiprotease imbalance. Am J Respir Crit Care Med 1999;160:S49–S52.[Abstract/Free Full Text]

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