Postpartum changes in the concentrations of IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), TGF-beta2, and prostaglandin E2 in 257 human milk samples collected longitudinally from 49 healthy mothers during the first 12 wk of lactation were determined by ELISA or RIA. The proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha were present in only a proportion of samples, and there was a wide range of concentrations detected at each time in the present study (IL-1beta, <15-400 pg/mL; IL-6, <15-1032 pg/mL; TNF-alpha, <15-2933 pg/mL). Concentrations of prostaglandin E2 increased after the first week and remained elevated for the remainder of the study (range, < 10-9966 pg/mL). The antiinflammatory cytokines TGF-beta1 (range, 43-7108 pg/mL) and TGF-beta2 (range, 208-57935 pg/mL) were present in substantial quantities in all samples, and there was little change in the mean concentration during 12 wk of lactation. The present study shows that immunomodulating agents are normally present in human milk in physiologically relevant quantities for at least the first 3 mo of the breast-fed infant's life.

Although epidemiological evidence is generally supportive of a causal association between respiratory syncytial virus (RSV) bronchiolitis during infancy and the development of persistent wheeze/asthma, if not allergy, the mechanism by which this occurs and an explanation for why all children do not succumb remains to be elucidated. Breast feeding has been found to confer a protective effect against respiratory infections such as RSV bronchiolitis and allergy; however, again there is little direct evidence and no clear mechanism. In this study, we examined whether human milk immunomodulatory factors (cells, cytokines) change in response to clinically diagnosed, severe bronchiolitis in the recipient breast-fed infant. We examined milk from 36 breast feeding mothers of infants hospitalized with bronchiolitis and compared them with milk from 63 mothers of postpartum age-matched healthy controls. Milks from mothers of infants hospitalized with bronchiolitis had significantly greater numbers of viable cells when compared with the milks obtained from mothers of healthy infants (1.3 +/- 0.4 vs. 0.3 +/- 0.03 x 10(6) cells/ml, mean +/- s.e.m.; p < or = 0.001). Further, the cells obtained from the mothers of infants hospitalized with bronchiolitis were found to produce a skewed cytokine profile ex vivo in response to stimulation by live RSV but not when cultured with a non-specific mitogen (concanavalin A). This study provides preliminary evidence for an immunological link between mothers and their breast-fed infants during severe respiratory infections as well as a possible contributing factor to the development of persistent wheeze in these infants.

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