Effect of interleukin-1 receptor antagonist on concanavalin A response of peripheral blood mononuclear cells from newborn calves.

The coexistence of interleukin (IL)-1beta with IL-1 receptor antagonist (ra) in bovine colostrum and the possibility of simultaneous transfer of these cytokines to neonates via colostrum have been demonstrated. In the present study, we investigated the effect of IL-1ra on the mitogenic response of calf peripheral blood mononuclear cells (PBMC) stimulated by concanavalin A (ConA), which was mediated by IL-1. Pretreatment of PBMC with recombinant bovine (rb) IL-1ra alone significantly suppressed the proliferation of ConA-stimulated cells. However, in the presence of rbIL-1beta, the suppressive activity of rbIL-1ra was counteracted. These results suggest that coexistence of IL-1ra with IL-1 in colostrum may have no effect on the activation of the neonatal immune system by IL-1beta.

Oral administration of IL-1 beta enhanced the proliferation of lymphocytes and the O(2)(-) production of neutrophil in newborn calf.

Recently, we demonstrated the presence of IL-1 beta in the colostral whey from dairy cows. Here, authors examined oral transmission of colostral IL-1 beta and its immunological effects on the neonatal calves. Biotin-labeled recombinant bovine (rb) IL-1 beta was administered orally to newborn calves and monitored in the serum. The results disclosed the passive transfer of colostral cytokines via the oral route, and a potent increase in white blood cell (WBC) count was observed in all calves administered with rbIL-1 beta. Oral administration of IL-1 beta significantly increased the proliferation of peripheral blood mononuclear cells (PBMCs) stimulated with concanavalin A, and the O(2)(-) production of stimulates neutrophils in newborn calves. These results suggest that the oral administration of IL-1 beta has an immunostimulatory activity in the newborn calf.

Detection of cytokines in bovine colostrum.

Colostrum contains factors that are protective for the neonate and may be a source of immunomodulary molecules that positively influence the immune status of the neonate. To confirm that colostrum contains a variety of cytokines with immunomodulatory properties, we established a bovine cytokine specific ELISA and five cytokines (IL-1 beta, IL-6, TNF-alpha, INF-gamma or IL-1 receptor antagonist, IL-1ra) in the whey samples from cows at different stages of lactation were monitored. The expression of cytokine mRNAs (IL-1 beta, IL-6, TNF-alpha and INF-gamma) in the colostral cells was detected by RT-PCR. The concentrations of cytokines in colostrum were significantly higher concentrations than those in the mature milk. A positive correlation was observed between the concentrations of IL-1ra and IL-1 beta in the colostrum samples. In conclusion, colostrum contains high levels of cytokines that could be produced and secreted in the mammary gland and that may have an immunomodulatory activity and influence neonatal immunity.

Detection of interleukin-1 beta in sera and colostrum of dairy cattle and in sera of neonates.

In order to obtain basic information about bovine interleukin-1 (IL-1 beta), levels of IL-1 beta in sera and milk of clinically normal mature Holstein cattle before and after parturition and in sera of newborn calves were examined by ELISA. The level of IL-1 beta was undetectable in sera of mature cattle around the time of artificial insemination, but the concentration gradually increased and reached a peak at parturition and then decreased again to an undetectable level. IL-1 beta in milk was detected on the day of parturition but not thereafter. IL-1 beta mRNA was detected by reverse transcription-polymerase chain reaction in the cells from milk collected during 20 days before and 2 to 3 days after parturition, but was not detected thereafter. Although IL-1 beta was not detected in all the sera of newborn calves, the concentration transiently increased with peak titers on day 3 and became undetectable by day 14 after birth. Newborns that showed serum IL-1 beta on day 3 had been fed on colostrum in which the IL-1 beta concentration was significantly higher than that in colostrum that had been fed to newborns having no detectable IL-1 beta on day 3. These results indicate that IL-1 beta is induced in association with pregnancy in healthy dairy cattle and that the cytokine might be transferred to neonates via colostrum.