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Cytokines in Pulmonary Emphysema: Can Results in Mice Be Translated to Humans?

We read and appreciated the article by Hoshino and colleagues (1) about the role of the cytokines IL-13 and IL-18 in pulmonary inflammation and emphysema. In their study, constitutive overproduction of IL-18 in the lungs of transgenic mice resulted in severe emphysema lesions, through an up-regulation of IL-13. These changes were independent of IFN- gene expression. The authors speculate that IL-18 may be a therapeutic target in chronic obstructive pulmonary disease.

We would agree with the authors that IL-18 and IL-13 may play a critical role in pulmonary inflammation and emphysema in mice (1, 2). However, we would suggest that the authors be very cautious when translating results in mice to humans. For example, since lung overexpression of IFN- or IL-13 in mice induces emphysema-like lesions (2, 3), our group has previously evaluated the expression of IL-13 and IFN- in lung samples from patients with emphysema, according to their smoking status (4). Contrary to results in mice, we found a similar expression of IFN- in patients with or without emphysema, but a reduced lung IL-13 content in patients with tobacco-induced severe emphysema (4). We did not assess lung expression of IL-18, and we are very interested in experiments that Hoshino and colleagues are conducting in patients with chronic obstructive pulmonary disease.

Marcel Bonay, Anne Boutten and Bruno Crestani

INSERM U 700, Université Paris 7
Hôpital Bichat-Claude Bernard
Assistance Publique-Hôpitaux de Paris (AP-HP)
Paris, France

FOOTNOTES

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. Hoshino T, Kato S, Oka N, Imaoka H, Kinoshita T, Takei S, Kitasato Y, Kawayama T, Imaizumi T, Yamada K, et al. Pulmonary inflammation and emphysema: role of the cytokines IL-18 and IL-13. Am J Respir Crit Care Med 2007;176:49–62.[Abstract/Free Full Text]
2. Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ, Chapman HA, Shapiro SD, Elias JA. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J Clin Invest 2000;106:1081–1093.[Medline]
3. Ma B, Kang MJ, Lee CG, Chapoval S, Liu W, Chen Q, Coyle AJ, Lora JM, Picarella D, Homer RJ, et al. Role of CCR5 in IFN-gamma-induced and cigarette smoke-induced emphysema. J Clin Invest 2005;115:3460–3472.[CrossRef][Medline]
4. Boutten A, Bonay M, Laribe S, Lesèche G, Castier Y, Leçon-Malas V, Fournier M, Durand G, Aubier M, Dehoux M, et al. Decreased expression of interleukin 13 in human lung emphysema. Thorax 2004;59:850–854.[Abstract/Free Full Text]

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