EFFECT OF MELATONIN ON ACTIVATED MACROPHAGE TNF, IL-6, AND REACTIVE OXYGEN INTERMEDIATES

Melatonin has recently been investigated as a biological response modi fier in sepsis and hypovolemic shock, Although melatonin is reported t o influence a variety of inflammatory and immune responses, evidence s upporting its effects on important macrophage-derived mediators is inc omplete. This study was designed to determine whether melatonin alters the release TNF, IL-6, and reactive oxygen intermediates by activated macrophages, TNF and IL-6 bioactivity in LPS-stimulated Wistar rat al veolar macrophage and RAW 264.7 cell culture supernatants were unchang ed by pretreatment with melatonin. Similarly, macrophage production of reactive oxygen intermediates, including H2O2 and superoxide anion, w ere unaffected by melatonin pretreatment. PMA-stimulated H2O2 producti on was determined in rat alveolar macrophages and RAW 264.7 cells. Sup eroxide anion generation was determined in the rat alveolar macrophage NR8383 cell line. Melatonin, at concentrations ranging from 10(-7) to 10(-4) M, does not alter LPS-stimulated TNF and IL-6, or PMA-stimulat ed H2O2 and superoxide anion production by the macrophage populations studied. These observations are in contrast to previous reports. Furth er studies are necessary to determine whether melatonin indirectly inf luences macrophage function by actions on nonmacrophage cell populatio ns.