Abstract
To determine whether human milk contained soluble receptors and cytokine antagonists that might contribute to its anti-inflammatory properties, ELISA and enzyme-amplified sensitivity immunoassay methods were used to quantitate soluble intercellular and vascular cell adhesion molecules, soluble E-selectin, soluble IL-6 receptor, IL-1 receptor antagonist, and soluble tumor necrosis factor-α (TNF-α) receptors I and II in human milk and colostrum. Soluble adhesion receptors (soluble intercellular and vascular cell adhesion molecules and soluble E-selectin) were present in colostrum at levels approximately equal to serum, whereas milk levels were significantly lower. Both colostrum and milk contained soluble IL-6 receptor, but the levels present were significantly lower than that reported for serum. The colostrum contents of IL-1 receptor antagonist (672 ± 202 pg/mL), TNF-α receptor I (>3703 ± 305 pg/mL), and TNF-α receptor II(>4507 ± 770 pg/mL) were significantly elevated over serum/plasma levels. Milk levels of IL-1 receptor antagonist and TNF-α receptor I were also greater than serum/plasma levels, but lower than colostrum levels. Examination of sequential milk specimens collected from seven women over a period of 2-6 mo showed that IL-1 receptor antagonist and TNF-α receptors I and II persisted throughout lactation. Column chromatographic fractionation of colostrum and milk demonstrated that soluble TNF-α receptors I and II had molecular sizes up to 60 kD, suggesting that they might be associated with other molecules. Antigen assays for TNF-α in colostrum and milk, as well as chromatographic fractionation experiments, showed that, although present, most TNF-α was not “free” in colostrum or milk, consistent with the observed content of soluble TNF-α receptors I and II. These studies demonstrate that human milk and colostrum contain soluble receptors and cytokine antagonists, materials which could contribute to their anti-inflammatory properties.
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Abbreviations
- sICAM-1:
-
soluble intercellular adhesion molecule-1
- sVCAM-1:
-
soluble vascular cell adhesion molecule-1
- sE-selectin:
-
soluble E-selectin
- sIL-6R:
-
soluble IL-6 receptor
- TNF:
-
tumor necrosis factor
- sTNF RI:
-
soluble tumor necrosis factor-α receptor I
- sTNF RII:
-
soluble tumor necrosis factor-α receptor II
- IL-1RA:
-
IL-1 receptor antagonist
- EASIA:
-
enzyme-amplified sensitivity immunoassay
- HRP:
-
horseradish peroxidase
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Acknowledgements
The authors thank Rosa Lee Hewitt, R.N., Debra Oelberg, R.N., and Patti Lundy, R.N., for their efforts and persistence in collecting colostrum and milk samples, and thank Medela, Inc., for the use of the breast pump used to collect milk for these studies. In addition, we thank Larry K. Pickering, M.D., for supplying the longitudinally collected milk samples examined in these studies and Penney Koeppen for her technical assistance.
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Supported by National Institute of Child Health and Human Development Grant HD 13021-11.
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Buescher, E., Malinowska, I. Soluble Receptors and Cytokine Antagonists in Human Milk. Pediatr Res 40, 839–844 (1996). https://doi.org/10.1203/00006450-199612000-00011
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DOI: https://doi.org/10.1203/00006450-199612000-00011
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