Measles virus infection leads to immune suppression. A potential mechanism is the reduction of interleukin 12 (IL-12) secretion during acute measles, resulting in a TH2 response. Studies in humans have reported conflicting results, detecting either a TH2 or a TH1 response. We have investigated the correlation between a TH2 response and immune suppression in specific-pathogen-free inbred cotton rats which were infected with measles vaccine and wild-type viruses. After infection of bone marrow-derived macrophages with wild-type virus, IL-12 secretion was reduced in contrast to the level for vaccine virus infection. In bronchoalveolar lavage cells, IL-12 secretion was suppressed after infection with both wild-type and vaccine virus on days 2, 4, and 6 and was detectable on days 8 and 10. After stimulation of mediastinal lymph node and spleen cells with UV-inactivated measles virus at various time points after infection, gamma interferon but no IL-4 was found. After stimulation with phorbol myristate acetate-ionomycin, high gamma interferon and low IL-4 levels were detected. To investigate whether the secretion of IL-4 contributes to immune suppression, a recombinant vaccine virus was created which secretes cotton rat IL-4. After infection with this recombinant virus, IL-4 secretion was enhanced. However, neither inhibition of concanavalin A-stimulated spleen cells nor keyhole limpet hemocyanin-specific proliferation of spleen cells was altered after infection with the recombinant virus in comparison to the levels with the parental virus. Our data indicate that measles virus infection leads to a decrease in IL-12 secretion and an increase in IL-4 secretion, but this does not seem to correlate with immune suppression.Acute measles is caused by infection with measles virus (MV) and is associated with high morbidity and mortality. The main reason for these is thought to be immune suppression due to MV infection. Studies addressing the mechanism of immune suppression have found evidence for a number of possible mechanisms. These include unidentified soluble mediators (10,39,40), interference with the type I interferon (IFN) system (for a review, see reference 9), apoptosis (8), impaired lymphoproliferation (23, 35), interleukin 12 (IL-12) downregulation (1, 18), and impaired dendritic cell (DC) function (36). Some of the mechanisms may operate in conjunction with each other; e.g., it is possible that the downregulation of IL-12 might lead to the development of a T-helper 2 (TH2) response that results in impaired lymphoproliferation. The evidence for this line of argument is that human macrophages, after stimulation through Toll-like receptor 4 (TLR-4), secrete less IL-12 when infected with MV (18). In MV-infected humans, the percentage of IL-12-expressing macrophages is reduced (1), and in Rhesus macaques, lowered serum levels of IL-12 have been found during MV infection (31). In macaques, this correlates with an increase of eosinophils in peripheral blood, indicative of increased secretion of .In serum or supernatants ...