Mammalian milk possesses inherent antimicrobial properties that have been attributed to several diverse molecules. Recently, antimicrobial peptides that belong to the cathelicidin gene family have been found to be important to the mammalian immune response. This antimicrobial is expressed in several tissues and increased in neonatal skin, possibly to compensate for an immature adaptive immune response. We hypothesized that the mammary gland could produce and secrete cathelicidin onto the epithelial surface and into milk. Human cathelicidin hCAP18/ LL-37 mRNA was detected in human milk cells by PCR. Quantitative real-time PCR demonstrated an increase in relative expression levels at 30 and 60 d after parturition. Immunohistochemistry of mouse breast tissue identified the murine cathelicidin-related antimicrobial peptide in lobuloacinar and ductules. Western blot analysis of human milk showed that LL-37 was secreted and present in the mature peptide form. The antimicrobial activity of LL-37 against Staphylococcus aureus, group A Streptococcus, and enteroinvasive Escherichia coli O29 in the human milk ionic environment was confirmed by solution colony-forming assay using synthetic peptide. These results indicate that cathelicidin is secreted in mammary gland and human milk, has antimicrobial activity against both Gram-positive and Gram-negative bacteria, and can contribute to the anti-infectious properties of milk. Antimicrobial peptides are found throughout nature and are important for the immune defense of plants, insects, and animals (1). Most of these molecules have a broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi, and viruses. In mammals, peptides from the cathelicidin family assist the antimicrobial efficacy of neutrophils, macrophages, and mast cells (2-6). In addition, antimicrobial genes of the defensin and cathelicidin families are produced by epithelia in response to injury of lung, gut, urinary bladder, oral mucosa, and skin (7-9). At the interface with the external environment, these molecules serve as a rapid first-line defense for inhibition of microbial proliferation and invasion.Human milk contains various anti-infectious materials such as immunoglobulins, cellular components, and cytokines. It is believed that these molecules contribute to decreased morbidity and mortality of infants who are fed breast milk (10,11). Recently, peptide antibiotics have been isolated from human milk, providing additional evidence that multiple molecules can be involved in the immune defense of this material (12,13). In other systems, the clinical consequences of antimicrobial peptide expression have been observed in patients who have atopic dermatitis and are susceptible to infection and also lack the ability to increase the cathelicidin LL-37 and human ␤-defensin (hBD-2) in response to inflammatory stimuli (14). Furthermore, patients with Kostmann syndrome, a rare inherited disorder characterized by frequent infections and neutrophil dysfunction, also have a deficien...

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