LACK OF IL-1 RECEPTOR ANTAGONISTIC ACTIVITY OF THE CAPSULAR F1 ANTIGEN OF YERSINIA-PESTIS

Because capsular Fl antigen of Yersinia pestis is reported to share se quence homology with interleukin-l receptor antagonist (IL-1ra), we in vestigated the potential IL-1 receptor antagonistic activity of Fl on human endothelial cells (EC). The biological activities of IL-1 recept or antagonist (IL-1ra) or IL-1ra-like molecule were measured by its ab ility to suppress the IL-1 beta-mediated induction of adhesion molecul es (ICAM and ELAM) on EC and of IL-6 secretion by these cells. Two dif ferent, purified, immunogenic and biologically active preparations of Fl, at concentrations up to 10-fold higher than that of IL-1ra, did no t exhibit any inhibitory activities of IL-1ra. These Fl preparations a lso did not activate peripheral blood mononuclear cells to produce IL- 4 or IL-10, cytokines which might downregulate pro-inflammatory cytoki ne production in response to infection. Thus, even though there is a h igh degree of similarity between Fl antigen and IL-1ra in three-dimens ional structure by computer modeling and sequence homology, our work i ndicates that F1 antigen of Y. pestis does not have IL-1ra-like activi ty. (C) 1998 Elsevier Science B.V. All rights reserved.