Determinants of susceptibility to sepsis and mortality: Malnutrition vs anergy

This study investigated whether increased susceptibility to sepsis and mortality is best determined by the nutritional state or by depressed host resistance, as indicated by anergy. One hundred and fifty Sprague-Dawley rats, 120–130 g, were presensitized with keyhole limpet hemocyanin (KLH) and fed a normal diet. At 3 weeks all rats had a reactive delayed-hypersensitivity skin test (DTH) response to KLH. Thirty rats were continued on this diet (Group I) and the rest were fed a 0.2% protein deficient diet. After 5 weeks of protein depletion 30 rats that maintained reactive DTH responses formed Group II and 30 rats that were anergic, as defined by a DTH response to KLH of < 5 mm induration at 24 hr, formed Group III. Carcass nitrogen studies confirmed that malnourished Groups II and III were comparably malnourished. All three groups were then challenged, via intraperitoneal injection, with a suspension of bacteriae and 10% BaSO₄ (total 2.5 cc/100 g) at three doses. There was no significant difference in survival between nourished reactive (78%) and malnourished reactive (60%) rats. However, malnourished anergic rats had a significantly higher mortality (80%) compared to nourished reactive rats (22%, χ² = 6.34, P < 0.025). Furthermore, a 40% difference in survival was observed between severely malnourished anergic and malnourished reactive DTH populations. We conclude that, while protein deprivation produces the state of anergy, survival from peritonitis challenge is determined, not by the malnutritional status per se, but by the adversely affected host immune state.