Soluble receptors and cytokine antagonists in human milk.
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-alpha (TNF-alpha) 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-alpha receptor I (> 3703 +/- 305 pg/mL), and TNF-alpha receptor II (> 4507 +/- 770 pg/mL) were significantly elevated over serum/plasma levels. Milk levels of IL-1 receptor antagonist and TNF-alpha 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-alpha receptors I and II persisted throughout lactation. Column chromatographic fractionation of colostrum and milk demonstrated that soluble TNF-alpha receptors I and II had molecular sizes up to 60 kD, suggesting that they might be associated with other molecules. Antigen assays for TNF-alpha in colostrum and milk, as well as chromatographic fractionation experiments, showed that, although present, most TNF-alpha was not "free" in colostrum or milk, consistent with the observed content of soluble TNF-alpha 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.
Buescher
E S
ES
Department of Pediatrics, Eastern Virginia Medical School, Children's Hospital of The King's Daughters, Norfolk, USA.
Malinowska
I
I
D015703:Antigens, CD / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000032:analysis*; D003126:Colostrum / Q000737:chemistry / Q000276:immunology*; D016207:Cytokines / Q000037:antagonists & inhibitors*; D019040:E-Selectin / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D053590:Interleukin 1 Receptor Antagonist Protein; D007774:Lactation; D008895:Milk, Human / Q000737:chemistry / Q000276:immunology*; D018123:Receptors, Interleukin / Q000032:analysis*; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012680:Sensitivity and Specificity; D012795:Sialoglycoproteins / Q000032:analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1