FOSFOMYCIN (FOM 1 R-2S-EPOXYPROPYLPHOSPHONIC ACID) SUPPRESS THE PRODUCTION OF IL-8 FROM MONOCYTES VIA THE SUPPRESSION OF NEUTROPHIL FUNCTION

We investigated the influence of fosfomycin (FOM) on the production an d the mRNA expression of interleukin-X (IL-8) by monocytes, In the inc ubation of whole blood stimulated by N-Formyl-Met-Leu-Phe (FMLP), FOM significantly suppressed the production and the mRNA expression of IL- 8 by monocytes and its inhibitory action was concentration-dependent ( FOM: 50-200 mu g/ml). However, FOM did not influence the production an d the mRNA expression of IL-8 in the incubation of fractionated mononu clear cell stimulated by FMLP. The supernatant of FMLP-stimulated poly morphonuclear leukocyte (PMNL) could induce the mRNA expression of IL- 8 by monocyte. The supernatant of FMLP-stimulated PMNL which was pre-t reated with FOM significantly (P < 0.05) inhibited the expression of I L-8 mRNA by monocyte. Moreover, FOM suppressed the production of leuko triene B-4 (LTB4) from neutrophil in a concentration-dependent manner. When LTB4 was added to the fractionated mononuclear cells directory, the expression of IL-8 mRNA was enhanced (P < 0.05). The present study indicated that FOM suppress the production of LTB4 from neutrophils a nd suppress the expression of IL-8 mRNA by LTB4 from monocytes. It was also demonstrated that LTB4 produced by neutrophil is one of the fact or which promotes the expression of IL-8 mRNA in monocytes. (C) 1998 E lsevier Science B.V. All rights reserved.