Malnutrition modifies pig small intestinal inflammatory responses to rotavirus

Infectious diarrheal diseases and malnutrition are major causes of child mo rbidity and mortality. In this study, malnutrition was superimposed on rota virus infection in neonatal piglets to simulate the combined intestinal str ess of viral enteritis in malnourished infants. Two-day-old piglets were as signed to three treatment groups as follows: 1) noninfected, fully nourishe d; 2) infected, fully nourished; and 3) infected, malnourished. Intestinal indices of inflammation were monitored over the subsequent 2-wk period. Int estinal damage and diarrhea were observed within 2 d of rotavirus infection and began to subside in nourished piglets by d 9 but persisted through d 1 6 postinfection in malnourished piglets. Rotavirus upregulated small intest inal expression of major histocompatibility complex (MHC) class I and class II genes; malnutrition intensified MHC class I gene expression and suppres sed MHC class II expression. Jejunal CD4(+) and CD8(+) T-lymphocyte numbers were elevated for infected, nourished piglets on d 2, 9 and 16 postinfecti on. Malnutrition did not significantly affect the local expansion of T cell subsets in response to rotavirus. Intestinal prostaglandin E-2 (PGE(2)) co ncentrations were elevated early after rotavirus infection independent of n utritional state, By d 9, PGE(2) concentrations returned to baseline in inf ected, nourished piglets but remained elevated in malnourished piglets, cor responding to diarrhea observations. Together, the results identify intesti nal indices of inflammation that are modulated by malnutrition and prompt r econsideration of current models of rotavirus pathophysiology.