ANTIGEN PRESENTATION IN PROTEIN-ENERGY MALNUTRITION

Protein-energy malnutrition is associated with intrinsic defects in macrophage (MO) microbicidal function, but effects on MO-CD4(+) cell interaction are unclear. This study examined the effect of protein-energy malnutrition on components of Ag presentation (AP) by peritoneal macrophages (PMO) and splenocyte responses (MLR) in the naive (resident) and infected state (mycobacterium-BCG), and assessed the potential role of prostaglandin (PGE(2)) and L-arginine-derived nitric oxide (NO.) as regulatory mechanisms in these immune interactions. Mice were randomized to receive either a control(24% casein, RD) or low-protein (2.5% casein, LPD) diets for 8 weeks. PMO and splenocytes were harvested and AP function and MLR assessed +/-N-G-monomethyl-L-arginine (NMMA; competitive inhibitor of NO. synthesis) or indomethacin (PGE(2) inhibitor). PMO components of AP were evaluated, including phagocytic function, MHC-class II (Ia) expression, and interleukin-1 (IL-1) and interleukin-6 (IL-6) production. PGE(2) production and NO. (measured as NO2-) synthesis were also assessed. AP and MLR were preserved in protein-energy malnutrition in both resident and activated states. BCG infection in RD was associated with PMO activation as measured by increased O-2(-) and NO2- release, but impaired AP and MLR responses. NMMA and indomethacin enhanced AP and MLR in RD groups only. Individual components of PMO AP (phagocytosis, IL-1 and IL-6 production) were defective during protein-energy malnutrition, as were NO2- and PGE(2) production. Thus, AP and MLR were preserved in LPD groups which may be related to a loss of prostaglandin- and L-arginine-mediated suppressor mechanisms. (C) 1995 Academic Press, Inc.