SYNERGISTIC EFFECT OF IMMUNOREGULATORY CYTOKINES ON PERIPHERAL-BLOOD MONOCYTES FROM PATIENTS WITH INFLAMMATORY BOWEL-DISEASE

Active inflammatory bowel disease (IBD) is characterized by increased monocyte secretion of proinflammatory cytokines. Immunoregulatory cyto kines such as Interleukin (IL)-4, IL-10, and IL-13 are capable of inhi biting the proinflammatory cytokine response of activated monocytes. T he aim of our study was to determine the effect of different antiinfla mmatory cytokines under various culture conditions and to evaluate com binations of antiinflammatory cytokines in down-regulating monocyte re sponse in IBD. Peripheral monocytes from patients with active IBD were isolated and stimulated with pokeweed mitogen (PWM). IL-4, IL-10, IL- 13 and a combination of IL-4/IL-10 and IL-10/IL-13 were added at diffe rent concentrations and different times. Secretion of IL-1 beta and TN F-alpha was assessed using sandwich ELISA systems. There was a diminis hed down-regulation of TNF-alpha by IL-4 and IL-13 in IBD when the cyt okines were added at the time of stimulation, while there was a signif icantly higher down-regulation when monocytes were primed with these T h-2 cytokines 24 hr before activation. IL-10 plus IL-4 and IL-10 plus IL-13, respectively, inhibited the proinflammatory cytokine response o f monocytes as well as matured macrophages much more than IL-4, IL-10, or IL-13 alone. Even at suboptimal concentrations for each cytokine a lone, a combination of cytokines showed synergistic inhibitory effects . In summary, a combination of antiinflammatory cytokines is more effe ctive in down-regulating the response of activated monocytes than usin g the cytokines alone and thus may have a potential therapeutic benefi t for patients with IBD.