Treatment with anti-CD3 antibody (anti-CD3) causes transient diarrhea. In this issue of the JCI, Clayburgh et al. show that, in jejunum of mice injected with anti-CD3 or with TNF, fluid accumulation and changes in epithelial phenotype develop, the latter including an increase in the passive permeability to proteins, smaller solutes, and water and the endocytosis of the brush border Na+/H+ exchanger, thereby inhibiting Na+ absorption (a second cytokine, LIGHT, has the former effect, but not the latter) (see the related article beginning on page 2682). These phenotypic changes, by themselves, do not, however, explain increased fluid secretion. Since active anion secretion is not stimulated (in fact it is inhibited), a non–epithelial cell–mediated driving force must be present — most likely an increase in interstitial pressure due to an effect of TNF on capillary permeability, smooth muscle contractility, or both.
Influence of anti-CD3 or TNF on murine jejunal Na+ absorption, paracellular permeability, and fluid homeostasis.