it was a pleasure to read the report from dunham and coworkers   concerning the relationship between hypocholesterolemia and outcome in patients following severe trauma . although their study involved only 28 patients , these patients were severely injured ( injury severity score 31  9 ) and they required at least 7 days of mechanical ventilation . upon admission to the surgical intensive care unit the mean cholesterol level was only 119  44 mg / dl , as compared with the expected normal cholesterol level ( taken from a database ) of 201  17 mg / dl ( p < 0.001 ) . in the patients who died ( n = 3 ) , the final cholesterol values were 33% lower than their initial postinjury levels , whereas in patients who survived the final cholesterol levels had risen by 28% . interestingly , the initial postinjury levels were considerably higher in the three patients who died than in those who survived ( 175  62 mg / dl versus 112  37 mg / dl ) . although these results are impressive , it is unknown whether the expected ( preadmission ) cholesterol values used as control , which were acquired from the general population , are consistent with those observed in the trauma population . it would have been interesting to know the actual preadmission cholesterol levels ( obtained either retrospectively or through follow - up evaluation ) ; complete lipid profiles ( e.g. triglycerides , very - low - density lipoprotein , low - density lipoprotein [ ldl ] , high - density lipoprotein [ hdl ] ) , including how each was individually affected ; cytokine data ( especially tumor necrosis factor- , il-6 ) to correlate with cholesterol levels ; and nutritional status ( especially lipid intake ) of these patients . cholesterol levels either remained low or fell in 90% of patients presenting with an infection . this response was more often associated with infection than with traditional markers such as leukocyte response , which was positive in only 61% of patients . cholesterol levels also decreased with the onset of each organ system dysfunction ( ratio of arterial oxygen tension to fractional inspired oxygen < 350 , creatinine > 2.0 mg / dl , glucose > 120 mg / dl , bilirubin > 2.5 mg / dl , arterial bicarbonate  28 or  23 mmol / l ; p < 0.01 ) . hypocholesterolemia was first reported in 1911 , when chauffard and coworkers reported decreased cholesterol levels in patients who were in ' very bad general condition ' during the febrile phase of tuberculosis . in 1920 , kipp noted a relationship between the degree of hypocholesterolemia and the severity of infection . we were unable to identify other articles about hypocholesterolemia following injury or infection in the literature until 1980 , when an article by coombes and coworkers   was published that described the changes in lipoproteins after burn injury . those investigators observed a profound decrease in cholesterol levels within a few days of the burn , with the lowest values occurring between the days 6 and 10 . they noted that both ldl and hdl , which carry over 80% of the total cholesterol in humans , were both decreased . in contrast , triglyceride - rich very - low - density lipoproteins increased in the acute phase . of the various reasons offered for the hypocholesterolemia seen in critically ill and injured patients , especially those with sepsis , one that seems especially important is related to the ability of lipids and lipoproteins to bind to and neutralize bacterial endotoxin ( lipopolysaccharide [ lps ] ) . it has been noted that lps in blood binds to lps binding protein , activating the cell surface cd14 receptor . this stimulates the release of a cascade of proinflammatory cytokines , including tumor necrosis factor- , il-1 , and il-6 . if lps binds to lipoproteins ( e.g. cholesterol ) , then cytokine release is decreased . for example , transgenic mice with elevated hdl   or ldl concentrations   are protected against lethal endotoxemia and severe gram - negative infections . indeed , infusion of hdl blocked lps - induced cytokine production in rabbits   and protected against lethal doses of endotoxin in mice . the administration of hdl to human volunteers also blocks many of the effects seen with infusion of lps . clinical support was provided by gordon and coworkers , who recently ( 2001 ) reported low cholesterol and lipoprotein concentrations in 111 critically ill surgical patients . they noted that these levels correlated inversely with concentrations of il-6 , soluble il-2 receptor , and il-10 . those investigators suggested that hypolipidemia ( hypocholesterolemia ) is an independent predictor of clinical outcome in critically ill patients . they also implied that a vicious cycle is initiated in many critically ill patients with acute sepsis with an increased production of inflammatory cytokines , which then decreases lipid and lipoprotein concentrations and increases the susceptibility to lps . dunham and coworkers should be congratulated for their contribution to this growing body of evidence and its implications for future treatments . if there were a way to increase the low lipid concentrations in these patients , then this could be an important therapeutic option for preventing and treating sepsis . hdl = high - density lipoprotein ; il = interleukin ; ldl = low - density lipoprotein ; lps = lipopolysaccharide .