Enhanced cytokine production by milk macrophages following infection with respiratory syncytial virus

Abstract

Paired samples of milk and serum collected 3 days postpartum from 20 women were tested for the presence and level of interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) by enzyme immunoassay. The expression of these cytokine mRNAs in milk macrophages from eight donors were semiquantitatively analyzed by reverse transcriptase-polymerase chain reaction. The effects of respiratory syncytial virus (RSV) infection on cytokine production were determined in five samples of milk macrophages. Over 90% of the milk samples tested exhibited detectable levels of IL-1β, IL-6, and TNF-α. No IL-12 or IFN-γ activity was detected in the milk. IL-6 activity was weakly detected in about 45%, and TNF-α activity in about 10% of the serum samples tested. However, no IL-1β, IL-12, or IFN-γ activity was demonstrated in any of the serum samples. Milk macrophages from eight subjects all exhibited mRNA for IL-1β, TNF-α, and IL-6, and IFN-γ mRNA in six of eight subjects, although no IFNγ was detected in any of the 20 samples of milk tested. RSV exposure resulted in a 2- to 100-fold increase in the expression of IL-1β, IL-6, and TNF-α mRNA as well as cytokine protein. Although RSV infection enhanced the expression of IFN-γ mRNA, no detectable IFN-γ was produced by the milk macrophages. These observations suggest that the milk macrophages are actively engaged in the physiological production of IL-1β, IL-6, TNF-α, and IFN-γ in the mammary gland and continue to possess the capacity to increase production of these cytokines in response to RSV and possibly other viral infections.