The role of restricted food intake in the pathogenesis of cachexia in severe combined immunodeficient beige mice infected with Mycobacterium paratuberculosis.

A paired feeding experiment was conducted to investigate if reduced food intake is a reason for the body weight loss previously observed in severe combined immunodeficient beige (SCID bg) mice infected with Mycobacterium paratuberculosis. Mice were paired on the basis of age, litter and sex. One of each pair was injected intraperitoneally with 10(5) viable M. paratuberculosis organisms. The remainder served as uninfected pairfed mates. Each uninfected mouse was restricted to the amount of food (per gram body weight) that its infected paired mate ate in the previous 24 hour period starting at four weeks postinfection until 12 weeks postinfection when the mice were necropsied. The mean body weights of the two groups were not significantly different (p < 0.05) at the start of the experiment (infected 27.6 +/- 2.1 g, pairfed 27.3 +/- 3.4 g) but the pairfed group weighed less after 12 weeks of restricted food intake. Mycobacterium paratuberculosis was isolated from the spleen, liver, gut and fecal pellets of the infected but not the uninfected mice. Acid-fast bacilli were seen histologically in the liver, spleen and intestines of the infected mice only. Analysis of carcass compositions indicated that both infected and pairfed mice lost dry matter. Despite the loss in dry matter, the infected mice appeared to have maintained their body weights due to an increased retention of body water (presumably due to edema of inflammation). These results suggest that infection of SCID bg mice with M. paratuberculosis causes a reduction in their food intake (presumably due to reduced appetite) which, in turn, contributes to a loss in dry matter. We suggest that this loss in dry matter is one of the initial events that eventually lead to cachexia, and that it precedes the body weight loss that inevitably occurs in SCID bg mice chronically affected with M. paratuberculosis.