Modulation of monocyte chemokine production and nuclear factor kappa B activity by oxidants

Reactive oxygen species can directly damage tissue. In this setting, amplif ication of tissue damage also occurs through infiltration of inflammatory c ells either acutely or chronically. Several recent studies suggest that rea ctive oxygen species stimulate production of certain chemokines, which are potent chemoattractants for inflammatory cells. In the present study, we ex amined whether oxidants, generated by the combination of xanthine and xanth ine oxidase (X/XO), alter chemokine production by monocytes and U937 cells. Our findings demonstrate that X/XO stimulates monocytes, but not U937 cell s, to produce increased amounts of interleukin-8 (IL-8) and monocyte chemoa ttractant protein. This effect is attenuated by pretreatment with dimethyls ulfoxide (DMSO), a scavenger of hydroxyl radicals, but is not affected by s uperoxide dismutase or catalase, In contrast, X/XO-induced cytotoxicity, ev idenced by lactate dehydrogenase release, is mediated primarily by hydrogen peroxide, as catalase reverses this effect. Finally, exposure to X/XO caus es an increase in nuclear factor kappa B (NF-kappa B), and this effect is a ttenuated by DMSO, These studies suggest that reactive oxygen species can i nduce production of molecules that amplify inflammation through attraction of inflammatory cells, It appears the hydroxyl radical is the principal oxi dant species involved in stimulation of chemokine production.