Intestinal microbial translocation: immunologic consequences and effects of interleukin-4.

Abstract

Administration of a chemically defined, liquid, elemental diet (CDD) results in intestinal microbial translocation, but the immunologic consequences of this process are unclear. This study evaluated the effects of CDD feeding and interleukin-4 (IL-4) administration on mesenteric lymphocyte, peritoneal macrophage (PMO), and hepatic Kupffer cell (KC) functions. BALB/C mice (n = 60) were randomized to receive a paired feeding of regular diet (RD) or a CDD for 14 days. Mesenteric lymph nodes (MLN) and cecum were cultured for bacteria. Mixed lymphocyte response and cytotoxic T-lymphocyte function of MLN lymphocytes were assayed. PMO and KC were harvested to measure tumor necrosis factor production, macrophage binding of fluorescent-labeled lipopolysaccharide, and Candida albicans phagocytosis (CAP) and killing (CAK); KC-hepatocyte interaction was assessed by hepatocyte protein synthesis. In a second study 75 BALB/c mice received RD, CDD, and CDD+IL-4 (30,000 units/mouse intraperitoneally). MLN lymphocyte and PMO functions were measured and intestinal immunoglobulin A levels were determined. Oral feeding of a CDD resulted in significant impairment of mesenteric lymphocyte mixed lymphocyte response and cytotoxic T-lymphocyte functions and decreased PMO tumor necrosis factor production, fluorescent-labeled lipopolysaccharide binding, CAP, and CAK. KC function was preserved in CDD-fed mice. Administration of IL-4 significantly reduced the incidence of bacteria positive MLN and increased PMO superoxide production, CAP, CAK, and MLN lymphocyte mitogenesis. Use of IL-4 may be beneficial in situations where intestinal microbial translocation contributes to sepsis.