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Antimicrobial Agents and Chemotherapy, September 1999, p. 2170-2175, Vol. 43, No. 9
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A New Azole Derivative of 1,4-Benzothiazine Increases the Antifungal Mechanisms of Natural Effector Cells

Lucia Pitzurra,1 Renata Fringuelli,2 Stefano Perito,1 Fausto Schiaffella,2 Roberta Barluzzi,1 Francesco Bistoni,1 and Anna Vecchiarelli1,*

Microbiology Section, Department of Experimental Medicine and Biochemical Sciences,1 and the Institute of Drug Chemistry and Technology,2 University of Perugia, Perugia, Italy

Received 24 February 1999/Returned for modification 30 March 1999/Accepted 15 June 1999

The most widely used drug for treatment of candidiasis is fluconazole (FCZ). Recently, a new derivative of 1,4-benzothiazine, compound FS5, was developed. FS5 had an appreciable protective effect against murine candidiasis. The present study was designed to dissect the antifungal mechanisms triggered by FS5 and to establish whether this compound could enhance the antimicrobial abilities of natural effector cells. The results show that intraperitoneal injection of FS5 in mice (i) induced an increase in circulating neutrophil levels comparable to that observed in FCZ-treated mice; (ii) enhanced phagocytosis and the killing activities of macrophages (Mphi s) isolated from the spleen or peritoneal cavity, with the latter effect correlating with induction of nitric oxide synthesis and production by Mphi s; and (iii) increased the levels of expression and synthesis of tumor necrosis factor alpha. These results suggest that the compound-induced synthesis of antimicrobial and proinflammatory molecules by heterogeneous Mphi populations is part of the beneficial effect of FS5 exerted against murine candidiasis.

* Corresponding author. Mailing address: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Phone: 39-075-585-3407. Fax: 39-075-585-3400. E-mail: vecchiar{at}unipg.it.

Antimicrobial Agents and Chemotherapy, September 1999, p. 2170-2175, Vol. 43, No. 9
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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