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Actually, although the islet vascular area (IVA) considerably decreases while the infiltration progresses, at 15 weeks of age, the peri\u2010islet vascular bed is unexpectedly and significantly increased. On the contrary, the intra\u2010IVA is significantly decreased, due to vessel dilation. Later, by 20\u201325 weeks of age, a decrease of both IVA occur, due to a significant islet \u03b2 cell loss. Moreover, a dramatic fall of natural free radical scavenger values, which, in turn, exert an influence upon vessels, is observed. These effects are completely counteracted by the administration of IL\u20104, a Th2 protective cytokine; IL\u201010, another putative Th2 cytokine, exerts direct effects upon endothelial cell (EC) function, as shown by the increase of endothelial nitric oxide synthase (eNOS) mRNA transcripts and by the release of endothelial NO which, in turn, exert vasodilatory effects; moreover, this cytokine significantly upregulates adhesion molecules on endothelia. On the other hand, IL\u20101\u03b2, a Th1 proinflammatory cytokine, dramatically increases nitrite and nitrate levels, as well as inducible nitric oxide synthase (iNOS) transcripts and also upregulates islet ICAM\u20101 expression as well as circulating ICAM\u20101 levels. Taken together, our findings clearly show that cytokines and islet endothelia are directly involved in the pathophysiology of the disease. Their reciprocal influence gives new insight to understand the role of microvasculature during islet \u03b2 cell attack. J. Cell. Biochem. 86: 651\u2013664, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.10250","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T11:44:15Z","timestamp":1033904655000},"page":"651-664","source":"Crossref","is-referenced-by-count":19,"title":["Th1 and Th2 cytokines exert regulatory effects upon islet microvascular areas in the NOD mouse"],"prefix":"10.1002","volume":"86","author":[{"given":"Gianpaolo","family":"Papaccio","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco Aurelio","family":"Pisanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosita Di","family":"Montefiano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Graziano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael 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