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This hypothesis, however, is based entirely on results from <jats:italic>in vitro<\/jats:italic> studies, wherein IL\u201010 has been shown to inhibit Thl cytokine synthesis. In this study we have compared the regulatory effects of both IL\u20104 and IL\u201010 on the development of a more complex Thl effector function <jats:italic>in vivo<\/jats:italic>, the development of delayed\u2010type hypersensitivity (DTH) to <jats:italic>Leishmania major<\/jats:italic> in mice immune to <jats:italic>Leishmania.<\/jats:italic> The results revealed two findings unexpected from <jats:italic>in vitro<\/jats:italic> studies with Thl clones. First, optimal inhibition of the DTH response (up to 70 %), assessed by footpad swelling and leukocytic infiltration, required the combination of IL\u20104 and IL\u201010, indicating that these two activities synergized to inhibit DTH reactivity. Second, IL\u20104 inhibited interferon\u2010\u03b3 (IFN\u2010\u03b3) production by lymph node cells draining the site of antigen challenge as well as did IL\u201010. The combination of both cytokines was no more effective than either alone. The mechanism by which IL\u20104 and IL\u201010 acted to inhibit DTH responses did not appear to be through inhibition of IFN\u2010\u03b3 or tumor necrosis factor production as treatment with antibodies which neutralized these activities failed to inhibit DTH responses. Inhibition of the DTH with IL\u20104 and IL\u201010 is the most effective specific regulator of DTH responses reported and the only one capable of modulating tuberculin DTH. These data establish IL\u20104 and IL\u201010 as potent inhibitors of Thl effector function <jats:italic>in vivo<\/jats:italic> and suggest their utility in controlling deleterious Thl\u2010mediated inflammatory responses such as occur in some infectious and autoimmune diseases.<\/jats:p>","DOI":"10.1002\/eji.1830231147","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T18:30:29Z","timestamp":1172773829000},"page":"3043-3049","source":"Crossref","is-referenced-by-count":134,"title":["Interleukin\u20104 and interleukin\u201010 synergize to inhibit cell\u2010mediated immunity <i>in vivo<\/i>"],"prefix":"10.1002","volume":"23","author":[{"given":"Fiona","family":"Powrie","sequence":"first","affiliation":[]},{"given":"Satish","family":"Menon","sequence":"additional","affiliation":[]},{"given":"Robert L.","family":"Coffman","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,12,8]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"35","volume":"13","author":"Parish C. 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