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Dietary Restriction Impairs Neutrophil Exudation by Reducing CD11b/CD18 Expression and Chemokine Production
Shigeo Ikeda, MD;
Hideaki Saito, MD;
Kazuhiko Fukatsu, MD;
Tomomi Inoue, MD;
Ilsoo Han, MD;
Satoshi Furukawa, MD;
Takeaki Matsuda, MD;
Akio Hidemura, MD
Arch Surg. 2001;136:297-304.
Hypothesis Patients with malnutrition are susceptible to infection. Polymorphonuclear neutrophils (PMNs) are the major effector of the nonspecific immune response in host resistance to infection. Dietary restriction may impair PMN-mediated immunity in the peritoneal cavity by reducing PMN exudation, adhesion molecule expression on PMNs, and chemokine production.
Design Randomized study of murine glycogen-induced peritonitis with dietary restriction.
Setting University research laboratory.
Materials Male C57BL/6J mice.
Interventions Mice (N = 204) were assigned to ad libitum, moderate, and severe diet-restricted groups receiving mouse chow ad libitum (132 g/kg, 66 g/kg, and 33 g/kg daily for 7 days, respectively). After dietary restriction with or without 1 day of refeeding, mice were administered glycogen intraperitoneally to induce cell exudation.
Main Outcome Measures CD11b, CD18, and CD62L expressions on circulating PMNs, phagocytosis, and reactive oxygen intermediate production by exudative PMNs were measured after glycogen installation. The levels of PMN-specific chemokine, macrophage inflammatory protein 2 (MIP-2), in peritoneal lavage fluid were also measured. These parameters were measured after glycogen installation in the refeeding experiment.
Results Seven days of dietary restriction decreased CD11b/CD18 expression on circulating PMNs, MIP-2 levels in peritoneal lavage fluid, and subsequent PMN exudation into the peritoneal cavity early in peritonitis. Both CD11b and CD18 expression on circulating PMNs and MIP-2 levels correlated significantly with numbers of exudative PMNs. Seven days of dietary restriction also impaired phagocytosis, while up-regulating reactive oxygen intermediate production by exudative PMNs. Only 1 day of ad libitum refeeding normalized CD11b/CD18 expression with PMN exudation into the peritoneal cavity.
Conclusions Short-term dietary restriction impairs PMN exudation into local inflammatory sites in murine peritonitis by reducing CD11b/CD18 expression and MIP-2 production. Even brief nutritional replenishment in diet-restricted patients may improve host defense via restoring these PMN functions and chemokine production at local inflammatory sites.
From the Department of Surgery, Faculty of Medicine (Drs Ikeda, Fukatsu, Inoue, Han, Furukawa, Matsuda, and Hidemura), and Surgical Center (Dr Saito), The University of Tokyo, Tokyo, Japan.
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