Acutely malnourished weanling mice administered Flt3 ligand can support a cell-mediated inflammatory response

The main objective of this investigation was to determine whether, despite acute (wasting) deficits of dietary nitrogen and energy, weanling mice could respond to the dendritic cell hematopoietin, Fms-like tyrosine kinase 3 ligand (F1t3L), in terms of an index of cell-mediated inflammatory competence. Male and female C57BL/6J weanlings were used, initially 19 days of age, and malnutrition was produced using a nitrogen-deficient diet. In preliminary work ten daily subcutaneous 1.0 tig doses of murine FIt3L, comparable to a protocol effective in humans, expanded the splenic conventional dendritic cell compartment (CD11c(+)F4/80(-/low)) of healthy weanlings without affecting the numbers of lymphocytes, macrophages, or recoverable mononuclear cells. Two subsequent experiments showed that, despite advancing malnutrition, exogenous F1t3L was able both to exert its classic influence on splenic conventional dendritic cell numbers and to invigorate the attenuated primary splenic cell-mediated inflammatory response to sheep erythrocytes. A final experiment showed that the cytokine intervention did not affect dendritic cell maturity according to several phenotypic indices. The findings provide new support for the proposition that dendritic cell numbers are the first limiting factor in the weak cell-mediated immune competence of acute pre-pubescent malnutrition. More substantially, intervention with F1t3L sustained an inflammatory systemic immune character despite progressive weanling malnutrition and weight loss. This outcome provides new support of fundamental character for the Tolerance Model which posits that the cell mediated inflammatory incompetence of acute pre-pubescent protein and energy deficits is a regulated adaptive attempt, the antithesis of the classic paradigm of unregulated immunological attrition.