Effect of protein malnutrition and immunomodulation on immune cell populations

Malnutrition has deleterious effects on immune functions, which predispose to an increased risk of infection. To study the effect of protein malnutrition on such immune functions and resistance to infection, we divided C57BL/6 mice into three groups: (1) control-standard diet, (2) protein-malnourished for 14 days, and (3) protein-malnourished for 14 days followed by standard diet for 3 days. The animals were further divided into subgroups: (1) an untreated group, (2) a muramyl dipeptide (MDP)-treated group, and (3) an interferon-gamma (IFN-gamma)-treated group before cecal ligation and puncture (CLP). Malnourished mice had significantly (P less than 0.05) lower body weight, serum albumin, spleen/body weight, percentage of splenic macrophages with Ia expression (%MOIa), increased splenic T suppressor cells, and greater mortality after CLP. Refeeding plus IFN-gamma or MDP significantly increased %MOIa (P less than 0.05) and also abrogated the increase in splenic lymphocytes seen in the malnourished animals. The increase in splenic suppressor T cells was not affected by refeeding or immunomodulation. Mortality after CLP was increased from 15% in the controls to 85% in the malnourished group and was significantly decreased by refeeding, MDP, and the combination of refeeding plus immunomodulators (P less than 0.05). These data show that 14-day malnutrition adversely affected the immune response to infection and increased mortality from CLP. Refeeding and immunomodulation restored macrophage Ia expression without CLP but not after the procedure, despite the significant reduction in mortality. The use of immunomodulation in protein malnourished conditions may serve as an adjuvant role to nutritional support.