Changes in Cytokine Production after Measles Virus Vaccination: Predominant Production of IL-4 Suggests Induction of a Th2 Response

Abstract

Immunization with live measles virus vaccine produces transient depression of delayed-type hypersensitivity (DTH) skin test responses and mitogen-induced lymphoproliferation irrespective of the serostatus of the recipient of the vaccine. To investigate this immune suppression further we studied peripheral blood mononuclear cells (PBMC) from adults before ( N = 17) and at various times after ( N = 34) immunization with measles virus vaccine. PHA-induced lymphoproliferation was decreased after vaccine and this was partly reversed by supplementation with rIL-2. There was no change in the proportion of PBMC that were CD4 + T cells, CD8 + T cells, NK cells, or B cells as analyzed by flow cytometry. Supernatant fluids were collected from PBMC after 72 hr in culture. Analysis for cytokines after vaccination showed spontaneous production of high levels of IL-4 (vaccinees 99 ± 23; controls 5.6 ± 5.6 ng/ml, P = 0.031) and TNFα (vaccinees 140 ± 45; controls 42 ± 14 pg/ml, P = 0.072) accompanied by low levels of IFN-γ (vaccinees 1.3 ± 0.6; controls 14.3 ± 10.1 U/ml), IL-1α (vaccinees 111 ± 22; controls 442 ± 107 pg/ml, P = 0.0001), and PGE 2 (vaccinees 75 ± 39; controls 300 ± 72 pg/ml, P = 0.048). Increased amounts of IL-4 were also produced after stimulation with PHA (vaccinees 140 ± 25; controls 40 ± 40 ng/ml, P = 0.013) while levels of IFN-γ and soluble IL-2 receptor were similar to controls and levels of IL-1α (vaccinees 443 ± 67; controls 792 ± 118 pg/ml, P = 0.026) remained low. Addition of rIL-2 had little effect on these cytokine levels. These data suggest that Th2 cells producing IL-4 are preferentially activated by measles vaccine and may contribute to the immunologic abnormalities associated with immunization for measles and possibly other viral infections.