Castro-Navarro Irma, Pace Ryan M, Williams Janet E, Pace Christina D W, Kaur Harpreet, Piaskowski Julia, Aragón Alberto, Rodríguez Juan M, McGuire Mark A, Fernandez Leonides, McGuire Michelle K
Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, United States.
College of Nursing, University of South Florida, Tampa, FL, United States.
Front Immunol. 2025 Jan 17;15:1532432. doi: 10.3389/fimmu.2024.1532432. eCollection 2024.
Mastitis, an inflammatory condition affecting more than 25% of breastfeeding women, is usually associated with reduced milk secretion, pain, and discomfort, which often leads to early cessation of breastfeeding. Although the etiology of mastitis is multifactorial, a pro-inflammatory state of the mammary gland might be a risk factor. However, changes in milk composition, and specifically in the milk immune profile, prior to and during mastitis have not been well described. To help close this research gap, we documented the immune profiles of milk produced by both breasts of 10 women experiencing clinical (CM) and 8 women experiencing subclinical (SCM) mastitis during the week of sign/symptom development as well as the week prior and compared them with milk produced by 14 healthy controls. CM was defined as having signs/symptoms of mastitis, whereas SCM was presumed if the participant did not have signs/symptoms of CM, but her milk had a somatic cell count >400,000 cell/mL and/or sodium-to-potassium (Na/K) ratio >1.0. Concentration of 36 immune factors (including immunoglobulins, cytokines, chemokines, and growth factors) was quantified via immunoassays. Milk produced by women who developed CM had distinct immune profiles the week prior to diagnosis, particularly elevated concentrations of pro-inflammatory cytokine IL-1β and regulatory cytokines IL-2, IL-4 and IL-10. In contrast, immune profiles in milk produced by women with SCM did not differ from that produced by healthy women or those with CM the week prior to mastitis onset. Once mastitis appeared, marked changes in milk's immune profile were observed in both CM and SCM groups. CM was characterized by elevated concentrations of 27 compounds, including pro-inflammatory cytokines (IL-1β, IL-1ra, and TNFα) and chemokines (including IL-8, eotaxin, IP-10, MCP-1, MIP1α, and MIP1β), compared to healthy controls. Milk's immune profile during SCM was intermediate, showing higher levels of IL-6, IFNγ, and MCP-1 compared to healthy controls, suggesting a milder, more controlled immune response compared to CM. Only milk produced by the mastitis-affected breast had altered immune profiles. Further research is needed to determine if these differences in milk's immune profiles can be used to improve mastitis risk prediction prior to onset of symptoms.
乳腺炎是一种影响超过25%哺乳期女性的炎症性疾病，通常伴有乳汁分泌减少、疼痛和不适，这往往导致过早停止母乳喂养。尽管乳腺炎的病因是多因素的，但乳腺的促炎状态可能是一个危险因素。然而，乳腺炎发生之前和期间乳汁成分的变化，特别是乳汁免疫谱的变化，尚未得到充分描述。为了帮助填补这一研究空白，我们记录了10名患有临床乳腺炎（CM）的女性和8名患有亚临床乳腺炎（SCM）的女性在症状出现的那一周以及前一周双侧乳房分泌的乳汁的免疫谱，并将其与14名健康对照者分泌的乳汁进行比较。CM被定义为具有乳腺炎的体征/症状，而如果参与者没有CM的体征/症状，但她的乳汁体细胞计数>400,000个细胞/毫升和/或钠钾（Na/K）比值>1.0，则推测为SCM。通过免疫测定法定量36种免疫因子（包括免疫球蛋白、细胞因子、趋化因子和生长因子）的浓度。患CM的女性在诊断前一周分泌的乳汁具有独特的免疫谱，特别是促炎细胞因子IL-1β以及调节性细胞因子IL-2、IL-4和IL-10的浓度升高。相比之下，SCM女性分泌的乳汁的免疫谱与健康女性或乳腺炎发作前一周患CM的女性分泌的乳汁的免疫谱没有差异。一旦乳腺炎出现，在CM和SCM组中均观察到乳汁免疫谱的显著变化。与健康对照相比，CM的特征是27种化合物的浓度升高，包括促炎细胞因子（IL-1β、IL-1ra和TNFα）和趋化因子（包括IL-8、嗜酸性粒细胞趋化蛋白、IP-10、MCP-1、MIP1α和MIP1β）。SCM期间乳汁的免疫谱处于中间水平，与健康对照相比，IL-6、IFNγ和MCP-1水平更高，表明与CM相比，免疫反应更温和、更受控制。只有受乳腺炎影响的乳房分泌的乳汁的免疫谱发生了改变。需要进一步研究以确定乳汁免疫谱的这些差异是否可用于改善症状出现前的乳腺炎风险预测。
