ADMINISTRATION OF INTERLEUKIN-13 TO SIMIAN IMMUNODEFICIENCY VIRUS-INFECTED MACAQUES - INDUCTION OF INTESTINAL EPITHELIAL ATROPHY

Increase Th2 cytokine production may contribute to some clinical manif estations of HIV infection, and studies have suggested that IL-13 rath er than IL-4 is involved in these conditions. We directly tested this hypothesis by administrating IL-13 to SIV-infected macaques, SIV-infec ted rhesus macaques received a daily subcutaneous injection for 21 day s of either IL-13 (10 mu g/kg/day) or a placebo. The four macaques tre ated with IL-13 experienced body weight loss (9.95 +/- 0.71%) related to intestinal tract damage: they all suffered from a complete atrophy of duodenal villi. This was presumably due to premature epithelial cel l death: proliferating Ki67(+) cells in glandular crypts were as numer ous as in control animals, but many epithelial cells developed apoptos is. The duodenal mucosa was infiltrated with cells expressing CD56 and PEN5, two markers of NK cells, and there was a deregulation of local cytokine and chemokine production characterized by a decrease in IL-10 gene expression (25% of controls) and an increase in gene expression for IFN-gamma(4-fold control), MIP-1 alpha(8-fold control), and MIP-1 beta (13-fold control). Thus, IL-13 can induce digestive epithelial ce ll injury in vivo in primates infected with a retrovirus. Therefore? i ts role should be considered in digestive manifestations of HIV infect ion as well as in other disorders associated with intestinal epithelia l atrophy.