Hyperthermic enhancement of serum antimicrobial activity: Mechanism by which fever might exert a beneficial effect on the outcome of gram-negative sepsis

Abstract

We have previously demonstrated heightened antibiotic activity at temperatures at the upper end of the physiological range. In the present studies we examined the effect of physiological variations in temperature on the antibacterial activity of antibiotic-free pooled human serum by comparing serum minimal inhibitory and bactericidal titers for gram-positive and gram-negative bacterial strains at 33, 37, and 41° C. We observed a progressive rise in both minimal inhibitory and minimal bactericidal titers with temperature for all classes of gram-negative bacilli studied. However, gram-positive cocci were generally resistant to serum, even at the highest experimental temperature. Bacterial strains adapted to growth at temperatures normally encountered on body surfaces were more susceptible to the enhancing effect of hyperthermia on serum inhibition than were strains adapted to 37° C. In addition, in vitro adaptation of one bacterial strain to different temperatures within the physiological range resulted in readily apparent variations in colonial morphology. These in vitro observations indicated that serum antibacterial activity and bacterial morphology may vary in response to minor changes in either the temperature to which bacteria are adapted before examination or the temperature of the assay system. If similar principles operate in vivo, hyperthermically augmented serum antimicrobial activity might represent one mechanism by which fever exerts a beneficial effect on the outcome of gram-negative sepsis.