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Inhibition of leukotriene B4(LTB4) by recombinant interleukin-1 receptor antagonist (IL-1RA) on human monocytes
Authors:Pio Conti  Maria R. Panara  Renato C. Barbacane  Marcella Reale  Mauro Bongrazio  Roy A. Dempsey
Affiliation:(1) Immunology Division, Institute of Experimental Medicine, University of Chieti Medical School, via dei Vestini, 66100 Chieti;(2) Institute of Normal and Pathologic Cytomorphology, CNR, University of Chieti Medical School, Italy;(3) Departments of Molecular Immunoregulation and Cytokine Biochemistry, ENDOGEN, Inc., Boston, MA, USA
Abstract:Macrophages are a primary source of interleukin-1 (IL-1), a glycoprotein which plays an important and essential role in the immune response and inflammation. Cytokines stimulate many different cells to produce increasing amounts of arachidonic acid metabolites such as prostaglandins and leukotrienes. Recently, interleukin-1 receptor antagonist (IL-1ra), a natural inhibitor of IL-1 released by macrophages, has been reported to inhibit PGE2. In accordance with these data our results show that the pretreatment, for 60 min, of purified human peripheral monocytes with IL-1ra at different concentrations (0.25–250 ng/ml) inhibits, in a dose-dependent manner, the generation of LTB4 released after 10 min treatment with calcium ionophore A23187 (5 mgrM). The inhibition of LTB4 synthesis by hrIL-1ra suggests the possibility that this new glycoprotein plays a modulatory role in immunity and inflammation.
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