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Wumin Dong,¹ Frank W. Kari, ² MaryJane K. Selgrade,¹ and M. Ian Gilmour¹

¹Immunotoxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; ²Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

Abstract
Caloric restriction has been shown to alter a broad range of immunological end points in both experimental animals and humans. The objective of this study was to investigate the effect of short-term moderate feed restriction (25% reduction) on allergic immune responses in Brown Norway rats. After 3 weeks of acclimation to their feed regimens, rats were sensitized and 2 weeks later challenged with house dust mite (HDM) antigen via intratracheal instillation. Feed restriction resulted in lower levels of antigen-specific IgE in serum and reduced antigenspecific lymphoproliferative activity in pulmonary lymph nodes. Feed restriction also attenuated pulmonary inflammation, as evidenced by lower levels of lactate dehydrogenase and total protein, decreased infiltration of neutrophils and eosinophils, and reduced secretion of pro-inflammatory cytokine tumor necrosis factor (TNF) - in bronchoalveolar lavage fluid. In addition, feed restriction decreased TNF- secretion in serum and decreased mRNA expression of TNF- and interleukin-6 in pulmonary lymph nodes. We conclude that feed restriction strongly dampened the allergic immune responses to HDM in rats and that this attenuation was associated with decreased expression and secretion of pro-inflammatory cytokines. Key words: allergy, asthma, dust mites, eosinophil, feed restriction, IgE, immune response, inflammation, lung, T lymphocyte, tumor necrosis factor-. Environ Health Perspect 108:1125-1131 (2000) . [Online 1 November 2000]

http://ehpnet1.niehs.nih.gov/docs/2000/108p1125-1131dong/ abstract.html

Address correspondence to: F.W. Kari, National Institute of Environmental Health Sciences, MD F1-05, P.O. Box 12233, 111 T.W. Alexander Drive, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-2926. Fax: (919) 541-1460. E-mail: kari@niehs.nih.gov

We thank S. Gavett, G. Hatch, and D. Morgan for their helpful comments. We thank J. Richards for technical support and D. Doerfler for statistical assistance. This work was performed while W. Dong held a National Research Council-U.S. EPA Research Associateship.

The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency, nor the mention of trade names or commercial products constitute endorsement or recommendation for use.

Received 10 April 2000 ; accepted 24 July 2000.