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IL 4 (5\u2013100 U\/ml) failed to activate any of these M\u03a6 populations for killing of intracellular AM. However, in the presence of low concentrations of IFN\u2010\u03b3 (10\u201320 U\/ml), which alone caused only a slight or intermediate reduction of the number of intracellular parasites, IL 4 led to a dramatic increase of the parasite elimination by all M\u03a6 populations. In the case of resident peritoneal M\u03a6, the synergism of IFN\u2010\u03b3 and IL 4 required the incubation of the M\u03a6 with both cytokines or with IFN\u2010\u03b3 alone for at least 10 h prior to infection; adding both cytokines after infection of the M\u03a6 did not cause a significant reduction of the intracellular parasite burden. The synergistic effect of IL 4 and IFN\u2010\u03b3 was completely abrogated in the presence of anti\u2010IL 4 antibodies. Furthermore, there was no significant difference between M\u03a6 derived from either susceptible BALB\/c or from resistant C57BL\/6 mice. Evidence is presented that the synergistic action of IL 4 and IFN\u2010\u03b3 occurs via an L\u2010arginine\u2010dependent killing pathway. From these data we conclude that IL 4 provides a strong stimulus for the killing of intracellular <jats:italic>L. major<\/jats:italic> AM provided low concentrations of IFN\u2010\u03b3 are present. Also, IFN\u2010\u03b3 is apparently an important priming signal for the activation of resident M\u03a6 to eliminate intracellular AM.<\/jats:p>","DOI":"10.1002\/eji.1830210213","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T12:40:45Z","timestamp":1172752845000},"page":"327-333","source":"Crossref","is-referenced-by-count":58,"title":["Cytokine interactions in experimental cutaneous leishmaniasis. 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