ABSTRACT
Measles infection in infants is associated with severe complications, and secondary infections are attributed to generalized immunosuppression. Measles binding to its monocyte receptor down-regulates IL-12 which is expected to diminish Th1-like cytokine responses, including IFN-gamma. Whether young infants can be immunized effectively against measles is an important public health issue. We evaluated Ag-specific IL-12, IFN-gamma, and T cell responses of infants at 6 (n = 60), 9 (n = 46), or 12 mo (n = 56) of age and 29 vaccinated adults. IL-12 and IFN-gamma release by PBMC stimulated with measles Ag increased significantly after measles immunization in infants. IL-12 and IFN-gamma concentrations were equivalent in younger and older infants, but IL-12 concentrations were significantly lower in infants than in adults (p = 0.04). IL-12 production by monocytes was down-regulated by measles; the addition of recombinant human IL-12 enhanced IFN-gamma production by PBMC stimulated with measles Ag, but infant T cells released significantly less IFN-gamma than adult T cells under this condition. Of particular interest, the presence of passive Abs to measles had no effect on the specific T cell proliferation or IFN-gamma production after measles stimulation. Cellular immunity to measles infection and vaccination may be limited in infants compared with adults as a result of less effective IFN-gamma and IL-12 production in response to measles Ags. These effects were not exaggerated in younger infants compared with effects in infants who were immunized at 12 mo. In summary, infant T cells were primed with measles Ag despite the presence of passive Abs, but their adaptive immune responses were limited compared with those of adults.
Subject(s)
Interferon-gamma/biosynthesis , Interleukin-12/biosynthesis , Lymphocyte Activation/immunology , Measles Vaccine/immunology , T-Lymphocytes/immunology , Adult , Age Factors , Antibodies, Viral/biosynthesis , Antibodies, Viral/physiology , Epitopes, T-Lymphocyte/immunology , Humans , Immunity, Maternally-Acquired , Infant , Interleukin-12/antagonists & inhibitors , Interleukin-12/genetics , Interleukin-12/pharmacology , Lymphocyte Activation/drug effects , Measles Vaccine/pharmacology , Monocytes/immunology , Monocytes/metabolism , Monocytes/virology , Neutralization Tests , Phytohemagglutinins/immunology , Recombinant Proteins/pharmacology , Vaccines, Attenuated/immunology , Vaccines, Attenuated/pharmacologyABSTRACT
Sixty patients with active upper gastrointestinal bleeding were randomized to received either continuous intravenous infusions of vasopressin (29 patients) or placebo (31 patients) at a rate of 40 U/h. Six hours after beginning the study, 13 patients in the vasopressin group and 11 in the placebo group] had ceased bleeding (p = 0.46). By 24 hours. 17 patients in the vasopressin group and 14 in the placebo group had stopped bleeding (p = 0.30). Restriction of the analysis to patients bleeding from varices showed no advantage with vasopressin treatment after 6 or 24 hours. No consistent trend favoring use of vasopressin to stop hemorrhage was noted during the 30-month study period. There was little difference between the two groups in the number of patients needing surgery (13 on vasopressin, 18 on placebo; p = 0.30) or the number of deaths (eight on vasopressin, 11 on placebo; p = 0.51); the transfusion requirement was the same. In our patients, a continuous intravenous infusion of vasopressin neither controlled bleeding nor altered outcome.
