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.
First Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan. junbm1c@med.kurume-u.ac.jp
J
J
Honda
Y
Y
Okubo
M
M
Kusaba
M
M
Kumagai
N
N
Saruwatari
K
K
Oizumi
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005578:Fosfomycin / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007975:Leukotriene B4 / Q000378:metabolism / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
D000900:Anti-Bacterial Agents; D016209:Interleukin-8; D012333:RNA, Messenger; D007975:Leukotriene B4; D005578:Fosfomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine