Changes in ion transport in inflammatory disease

Abstract

Ion transport is essential for maintenance of transmembranous and transcellular electric potential, fluid transport and cellular volume. Disturbance of ion transport has been associated with cellular dysfunction, intra and extracellular edema and abnormalities of epithelial surface liquid volume. There is increasing evidence that conditions characterized by an intense local or systemic inflammatory response are associated with abnormal ion transport. This abnormal ion transport has been involved in the pathogenesis of conditions like hypovolemia due to fluid losses, hyponatremia and hypokalemia in diarrhoeal diseases, electrolyte abnormalities in pyelonephritis of early infancy, septicemia induced pulmonary edema, and in hypersecretion and edema induced by inflammatory reactions of the mucosa of the upper respiratory tract. Components of membranous ion transport systems, which have been shown to undergo a change in function during an inflammatory response include the sodium potassium ATPase, the epithelial sodium channel, the Cystic Fibrosis Transmembrane Conductance Regulator and calcium activated chloride channels and the sodium potassium chloride co-transporter. Inflammatory mediators, which influence ion transport are tumor necrosis factor, gamma interferon, interleukins, transforming growth factor, leukotrienes and bradykinin. They trigger the release of specific messengers like prostaglandins, nitric oxide and histamine which alter ion transport system function through specific receptors, intracellular second messengers and protein kinases. This review summarizes data on in vivo measurements of changes in ion transport in acute inflammatory conditions and in vitro studies, which have explored the underlying mechanisms. Potential interventions directed at a correction of the observed abnormalities are discussed.

Figure 1

Components of epithelial ion transport and their interactions [[+] = activating, [-]= inactivating].

Figure 2

Nasal potential difference in a child ventilated with meningococcal septicaemia related pulmonary edema. The graph shows a lack of response of chloride channels in airway epithelium to a low chloride solution. This response is restored by the addition of the beta receptor agonist isoprenaline to the perfusate [unpublished graph from work published in [11]]. A model of the components of the ion transport systems involved has been put next to it: [+] = activating.

Figure 3

Short-circuit measurements on healthy colonic mucosa and mucosa of a patient with ulcerative colitis [UC]. Shown is the response of the short circuit current (I_SC) to aldosterone [upregulator of ENaC and Na/K ATPase function] and amiloride [ENaC blocker] [Taken with permission from [89].