{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:42:05Z","timestamp":1774672925086,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,12,6]],"date-time":"2005-12-06T00:00:00Z","timestamp":1133827200000},"content-version":"vor","delay-in-days":4844,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1992,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mice immunized with attenuated <jats:italic>Salmonella typhimurium<\/jats:italic>, strain SL3235, while protected against virulent challenge, are unable to mount <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> antibody responses to non\u2010<jats:italic>Salmonella<\/jats:italic> antigens, such as tetanus toxoid and sheep red blood cells, and exhibit profoundly suppressed responses to B and T cell mitogens. Suppression of antibody responses is mediated by macrophage (M\u03d5)\u2010released soluble factors, and is completely reversed by treatment with interleukin (IL)\u20104. The present report identifies the suppressor factor as nitric oxide (NO), and provides evidence for a mechanism by which IL\u20104 abrogates suppression. Suppressed antibody responses correlated with high levels of NO secretion by splenocytes of SL3235\u2010immunized mice. NO production was observed only in cultures consisting of the adherent cell fraction of immune splenocytes. Further, immunosuppression was reversed by <jats:italic>N<\/jats:italic><jats:sup>G<\/jats:sup>\u2010monomethyl\u2010L\u2010arginine (NMLA), a competitive inhibitor of NO synthesis, and was completely blocked by the addition of excess L\u2010arginine. Treatment with IL\u20104, or anti\u2010interferon (IFN)\u2010\u03b3 monoclonal antibody (mAb), also abrogated suppression. Optimal reversal of suppression was observed only when NMLA, IL\u20104, or anti\u2010IFN\u2010\u03b3 mAb, was added at day 0 of the 5\u2010day plaque\u2010forming cell assay. Treatment with either IL\u20104 or anti\u2010IFN\u2010\u03b3 mAb also lead to a sharp inhibition of NO production by immune spleen cells. Moreover, the addition of IL\u20104 to splenic adherent M\u03d5 inhibited their ability to generate NO. Our data characterize an immunoregulatory pathway, involving IFN\u2010\u03b3 and NO, by which M\u03d5 mediate immunosuppression and identify IL\u20104 as a potent inhibitor of this pathway.<\/jats:p>","DOI":"10.1002\/eji.1830220911","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T17:49:44Z","timestamp":1172771384000},"page":"2249-2254","source":"Crossref","is-referenced-by-count":126,"title":["Immunosuppression induced by nitric oxide and its inhibition by interleukin\u20104"],"prefix":"10.1002","volume":"22","author":[{"given":"Basel K.","family":"Al\u2010Ramadi","sequence":"first","affiliation":[]},{"suffix":"Jr.","given":"Joseph J.","family":"Meissler","sequence":"additional","affiliation":[]},{"given":"Duan","family":"Huang","sequence":"additional","affiliation":[]},{"given":"Toby K.","family":"Eisenstein","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,12,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/152.1.171"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.4049\/jimmunol.136.5.1820","volume":"136","author":"Edwards C. 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