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 and the mRNA expression of interleukin-8 (IL-8) by monocytes. In the incubation 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 microg/ml). However, FOM did not influence the production and the mRNA expression of IL-8 in the incubation of fractionated mononuclear cell stimulated by FMLP. The supernatant of FMLP-stimulated polymorphonuclear leukocyte (PMNL) could induce the mRNA expression of IL-8 by monocyte. The supernatant of FMLP-stimulated PMNL which was pre-treated with FOM significantly (P < 0.05) inhibited the expression of IL-8 mRNA by monocyte. Moreover, FOM suppressed the production of leukotriene B4 (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 and suppress the expression of IL-8 mRNA by LTB4 from monocytes. It was also demonstrated that LTB4 produced by neutrophil is one of the factor which promotes the expression of IL-8 mRNA in monocytes.