Studies in Acid/Peptic Disorders
Peptic ulcer disease is a chronic illness whose hallmark is mucosal inflammation. In recent years, a variety of agents have been implicated in the pathophysiology of several chronic inflammatory diseases. The interleukins and tumor necrosis factor/cachectin are soluble factors (cytokines) that have been proposed as principal participants in mediating many of the mechanisms of tissue injury. There is some evidence that TNF-a and IL-1a play an important role in tissue repair. TNF-a is a potent angiogenic factor, suggesting it may act to remodel vasculature during tissue healing. Preliminary in vivo studies have shown that TNF-a and IL-1a inhibit gastric acid secretion, and are cytoprotective. Regardless of the factors responsible for development of a peptic ulcer, tissue injury and release of IL-1 and TNF-a could act as a physiologic brake to reduce acid secretion and limit further damage. The direct effects of these autokines on acid secretion can be studied in vitro using isolated parietal cells by measuring the accumulation of the weak base aminopyrine (AP) in acidic spaces within the cells as an index of secretory activity. We are examining the direct action of TNF-a and IL-1a on purified populations of parietal cells to determine the signal transduction pathways responsible for the inhibitor and cytoprotective effects of these cytokines.
Nompleggi D, et al. The effect of recombinant cytokines on [14C] aminopyrine accumulation in isolated canine parietal cells. J Pharmacol Exp Ther 270:440-445, 1994.