Lasting biological effects of early environmental influence. 3. Metabolic responses of mice to neonatal infection with a filterable weight-depressing agent.

Abstract

A lasting depression of body weight was consistently produced in SPF mice by infecting them orally 2 days after birth with a nonlethal, bacteria-free filtrate, prepared from the intestine of young SPF mice previously infected with an unidentified agent. Neonatal infection caused a decrease of muscle DNA and of muscle and brain protein in the adults. No other effect was detected in the chemical composition of various organs. Incorporation of (14)C-amino acid into the acid precipitable fractions of liver, kidney, muscle, and brain was lower in infected than in control animals. No difference in incorporation was recognized in the thymus and spleen. The free amino acid pool of adults, measured as blood levels of free amino nitrogen, was decreased by neonatal infection. Surprisingly, the food intake of young animals infected neonatally was higher than that of the controls, measured on the basis of body weight. Their fecal excretion of nitrogen was also higher. The comparative responses of infected and control adults to a stressful situation was measured by giving them intravenously the antituberculous vaccine BCG. Under these conditions, the mice infected neonatally excreted some 20% more nitrogen in their urine and 40% more in their feces than did the controls. The mechanisms through which neonatal infection caused a lasting weight depression are discussed in the light of these metabolic findings.