Cytokines in Human Milk: Properties and Potential Effects Upon the Mammary Gland and the Neonate

Overview

Journal J Mammary Gland Biol Neoplasia

Date 1996 Jul 1

PMID 10887499

Citations 26

Authors

A S Goldman

S Chheda

R Garofalo

F C Schmalstieg

Affiliations

Soon will be listed here.

Abstract

Epidemiologic and immunologic studies of breastfed and nonbreastfed infants and investigations of certain biologic activities in human milk led to the identification of immunomodulating agents in human milk. Among them were the cytokines interleukin-1 beta (IL-1 beta); IL-6, IL-8, IL-10, granulocyte-colony stimulating factor, macrophage-colony stimulating factor (M-CSF), tumor necrosis factor-alpha, interferon-gamma, epithelial growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and TGF-beta 2. Interferon-gamma may originate from T cells in milk; EGF, TGF-alpha, TGF-beta, M-CSF, IL-6, and IL-8 may be produced by mammary gland epithelium. Based upon their known functions, we hypothesize that cytokines influence the development and immunologic function of the mammary gland and the neonate. Those in vivo functions remain to be defined by future investigations.

Citing Articles

The Relationship Between Breast Milk Components and the Infant Gut Microbiota.

Boudry G, Charton E, Le Huerou-Luron I, Ferret-Bernard S, Le Gall S, Even S Front Nutr. 2021; 8:629740.

PMID: 33829032 PMC: 8019723. DOI: 10.3389/fnut.2021.629740.

Lactoferrin and Immunoglobulin Concentrations in Milk of Gestational Diabetic Mothers.

Lis-Kuberka J, Berghausen-Mazur M, Orczyk-Pawilowicz M Nutrients. 2021; 13(3).

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Human Cytomegalovirus (HCMV) Reactivation in the Mammary Gland Induces a Proinflammatory Cytokine Shift in Breast Milk.

Rabe T, Lazar K, Cambronero C, Goelz R, Hamprecht K Microorganisms. 2020; 8(2).

PMID: 32093317 PMC: 7074878. DOI: 10.3390/microorganisms8020289.

Temporal development of the infant gut microbiome.

Moore R, Townsend S Open Biol. 2019; 9(9):190128.

PMID: 31506017 PMC: 6769289. DOI: 10.1098/rsob.190128.

Association of reduced count of interleukin-13-producing cells in breast milk with atopic dermatitis in infancy.

Moradkhani S, Jafarzadeh A, Bazargan-Harandi N, Baneshi M, Mohammadi M Indian J Med Res. 2018; 148(3):317-322.

PMID: 30425222 PMC: 6251272. DOI: 10.4103/ijmr.IJMR_1682_16.

References

Dohlsten M, Hedlund G, Sjogren H, Carlsson R . Two subsets of human CD4+ T helper cells differing in kinetics and capacities to produce interleukin 2 and interferon-gamma can be defined by the Leu-18 and UCHL1 monoclonal antibodies. Eur J Immunol. 1988; 18(8):1173-8. DOI: 10.1002/eji.1830180805. View

Paolini J, Willard D, Consler T, Luther M, Krangel M . The chemokines IL-8, monocyte chemoattractant protein-1, and I-309 are monomers at physiologically relevant concentrations. J Immunol. 1994; 153(6):2704-17. View

Guglietta A, Lesch C . Effect of h-EGF and h-EGF 1-48 on histamine-stimulated gastric acid secretion in rats and monkeys. J Physiol Paris. 1993; 87(6):343-7. View

Houssiau F, Coulie P, Van Snick J . Distinct roles of IL-1 and IL-6 in human T cell activation. J Immunol. 1989; 143(8):2520-4. View

Goldenring J, Tsunoda Y, Stoch S, Coffey R, Modlin I . Transforming growth factor-alpha (TGF alpha) inhibition of parietal cell secretion: structural requirements for activity. Regul Pept. 1993; 43(1-2):37-47. DOI: 10.1016/0167-0115(93)90405-w. View

Wingfield P, Pain R, Craig S . Tumour necrosis factor is a compact trimer. FEBS Lett. 1987; 211(2):179-84. DOI: 10.1016/0014-5793(87)81432-1. View

Garofalo R, Chheda S, Mei F, Palkowetz K, Rudloff H, Schmalstieg F . Interleukin-10 in human milk. Pediatr Res. 1995; 37(4 Pt 1):444-9. DOI: 10.1203/00006450-199504000-00010. View

Sallerfors B . Endogenous production and peripheral blood levels of granulocyte-macrophage (GM-) and granulocyte (G-) colony-stimulating factors. Leuk Lymphoma. 1994; 13(3-4):235-47. DOI: 10.3109/10428199409056287. View

Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W . Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993; 75(2):263-74. DOI: 10.1016/0092-8674(93)80068-p. View

10.

Hill C, Osslund T, Eisenberg D . The structure of granulocyte-colony-stimulating factor and its relationship to other growth factors. Proc Natl Acad Sci U S A. 1993; 90(11):5167-71. PMC: 46676. DOI: 10.1073/pnas.90.11.5167. View

11.

Defrance T, Vanbervliet B, Briere F, Durand I, Rousset F, Banchereau J . Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. J Exp Med. 1992; 175(3):671-82. PMC: 2119142. DOI: 10.1084/jem.175.3.671. View

12.

Lindberg T, Ohlsson K, Westrom B . Protease inhibitors and their relation to protease activity in human milk. Pediatr Res. 1982; 16(6):479-83. DOI: 10.1203/00006450-198206000-00016. View

13.

Bauer J, Ganter U, Geiger T, Jacobshagen U, Hirano T, Matsuda T . Regulation of interleukin-6 expression in cultured human blood monocytes and monocyte-derived macrophages. Blood. 1988; 72(4):1134-40. View

14.

Perlmutter D, May L, Sehgal P . Interferon beta 2/interleukin 6 modulates synthesis of alpha 1-antitrypsin in human mononuclear phagocytes and in human hepatoma cells. J Clin Invest. 1989; 84(1):138-44. PMC: 303963. DOI: 10.1172/JCI114133. View

15.

Kobayashi Y, Oppenheim J, Matsushima K . Human pre-interleukin 1 alpha and beta: structural features revealed by limited proteolysis. Chem Pharm Bull (Tokyo). 1991; 39(6):1513-7. DOI: 10.1248/cpb.39.1513. View

16.

May L, Santhanam U, Sehgal P . On the multimeric nature of natural human interleukin-6. J Biol Chem. 1991; 266(15):9950-5. View

17.

FORSYTH I . The mammary gland. Baillieres Clin Endocrinol Metab. 1991; 5(4):809-32. DOI: 10.1016/s0950-351x(10)80016-3. View

18.

Schindler R, Mancilla J, Endres S, Ghorbani R, Clark S, Dinarello C . Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood. 1990; 75(1):40-7. View

19.

Hooton J, PABST H, Spady D, Paetkau V . Human colostrum contains an activity that inhibits the production of IL-2. Clin Exp Immunol. 1991; 86(3):520-4. PMC: 1554205. DOI: 10.1111/j.1365-2249.1991.tb02963.x. View

20.

Savino R, Lahm A, Giorgio M, Cabibbo A, Tramontano A, Ciliberto G . Saturation mutagenesis of the human interleukin 6 receptor-binding site: implications for its three-dimensional structure. Proc Natl Acad Sci U S A. 1993; 90(9):4067-71. PMC: 46447. DOI: 10.1073/pnas.90.9.4067. View