Interleukin 2 modulates intestinal epithelial cell function in vitro

Although interleukin 2 (IL-2) has been presumed to have a highly circumscribed range of target cells limited largely to classic immune cell populations, the presence of functional IL-2 receptors in rat epithelial cell lines has recently been demonstrated. Limited information is available about the functional effects of IL-2 on intestinal epithelial cells. The effect of recombinant IL-2 on intestinal epithelial cell migration was assessed using a previously described in vitro model of epithelial restitution by quantitation of cells migrating into standard wounds established in confluent IEC-6 cell monolayers. Transforming growth factor beta content was assessed by Northern blot and bioassay. Exogenous IL-2 enhanced epithelial cell restitution in vitro on average 3.8-fold; this effect was independent of cell proliferation. Enhancement of restitution through IL-2 could be completely blocked through antibodies directed against TGFbeta1 and interleukin-2 receptor, indicating that stimulation of epithelial cell restitution is specifically enhanced by interleukin-2 and mediated through a TGFbeta-dependent pathway. In addition, increased expression of TGFbeta1 mRNA and increased levels of bioactive TGFbeta peptide in wounded monolayers treated with IL-2 compared to unwounded monolayers cultured in serum-deprived medium alone support the notion that enhancement of epithelial cell restitution in vitro is mediated through a TGFbeta-dependent pathway. These studies suggest that IL-2, a potent cytokine whose biological origin and targets have been presumed to be largely limited to lymphocyte and macrophage populations, may play a role in preserving the integrity of the intestinal epithelium following various forms of injuries.