PMID- 3857019 OWN - NLM STAT- MEDLINE DCOM- 19850517 LR - 20210526 IS - 0066-4804 (Print) IS - 1098-6596 (Electronic) IS - 0066-4804 (Linking) VI - 27 IP - 2 DP - 1985 Feb TI - Enhancement by clofazimine and inhibition by dapsone of production of prostaglandin E2 by human polymorphonuclear leukocytes in vitro. PG - 257-62 AB - The effects of the antileprosy agents clofazimine and dapsone (1 to 10 micrograms/ml) on the spontaneous and stimulated release of prostaglandin E2 (PG E2) by human polymorphonuclear leukocytes (PMNL) in vitro have been investigated. PMNL were obtained from normal adult volunteers and three patients with leprosy (two borderline lepromatous and one subpolar lepromatous leprosy). The synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) at a concentration of 10(-7) M was used as the stimulant of PG E2 synthesis. None of the test agents at the concentrations used inhibited the binding of radiolabeled FMLP to PMNL. However, dapsone at 5 and 10 micrograms/ml inhibited the spontaneous and FMLP-induced release of PG E2 by PMNL. Clofazimine, on the other hand, significantly increased both the spontaneous and the FMLP-induced synthesis of PG E2 by PMNL. The enhancing effects of clofazimine on FMLP-mediated synthesis of PG E2 were particularly striking and were observed at concentrations of 1 to 10 micrograms of the drug per ml. Measurements of PMNL spontaneous and FMLP-induced synthesis of PG E2 in the presence of both clofazimine and dapsone (5 micrograms/ml) indicated that the two drugs are mutually antagonistic. PMNL from both normal control subjects and patients with leprosy were equally sensitive to these effects of clofazimine and dapsone. The immunostimulatory and immunosuppressive properties of dapsone and clofazimine, respectively, may be related to the opposite effects of these agents on PG E2 synthesis in human leukocytes. FAU - Anderson, R AU - Anderson R LA - eng PT - Journal Article PL - United States TA - Antimicrob Agents Chemother JT - Antimicrobial agents and chemotherapy JID - 0315061 RN - 0 (Prostaglandins E) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - 8W5C518302 (Dapsone) RN - D959AE5USF (Clofazimine) RN - K7Q1JQR04M (Dinoprostone) RN - VJT6J7R4TR (Rifampin) SB - IM MH - Clofazimine/*pharmacology MH - Dapsone/*pharmacology MH - Dinoprostone MH - Female MH - Humans MH - In Vitro Techniques MH - Kinetics MH - Male MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Neutrophils/drug effects/*metabolism MH - Prostaglandins E/*biosynthesis MH - Rifampin/pharmacology PMC - PMC176249 EDAT- 1985/02/01 00:00 MHDA- 1985/02/01 00:01 PMCR- 1985/02/01 CRDT- 1985/02/01 00:00 PHST- 1985/02/01 00:00 [pubmed] PHST- 1985/02/01 00:01 [medline] PHST- 1985/02/01 00:00 [entrez] PHST- 1985/02/01 00:00 [pmc-release] AID - 10.1128/AAC.27.2.257 [doi] PST - ppublish SO - Antimicrob Agents Chemother. 1985 Feb;27(2):257-62. doi: 10.1128/AAC.27.2.257.