Abstract 1539 Cytokines in Disease and Therapy Poster Symposium, Monday, 5/3

Host response to infection and other forms of injury is mediated by a complex interplay of pro- and anti-inflammatory cytokines. Temperature has been shown to affect in vitro cytokine production by adult macrophages. We studied the effects of hyper- and hypothermia on release of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 by lipopolysaccharide (LPS)-stimulated monocytes (monos) and monocyte-derived macrophages (macros) of adults (n=5) and term umbilical cord blood (n=4). Cells were treated with LPS (E. coli 055:B5) 100 ng/ml and cultured at 32°C, 37°C, 38.5°C, or 40°C. At 2, 6, and 24 hours, supernatants were removed and ELISA performed for TNF-α, IL-1β, and IL-6. Results (mean % of cytokine release relative to 37°C ± SE) Hyperthermia: At 40°C there was an early (2hr) burst of IL-1β (230% ± 51%) and IL-6 (260% ± 90%) from adult monos, and TNF-α (138% ± 11%) and IL-6 (187% ± 30%) from adult macros (all p<.05). A similar trend was seen in cord monos for TNF-α and IL-6. In contrast, after 24 hours at 40°C, cord and adult monocytes and macrophages released less TNF-α and IL-1βthan at 37°C: cord monos (TNF-α, 61% ± 4%; IL-1β, 67% ± 19%), cord macros (TNF-α, 56 ± 6; IL-1β, 61% ± 2%*), adult monos (TNF-α, 66% ± 4%*; IL-1β, 66% ± 24%), adult macros (TNF-α, 66% ± 4%*; IL-1β, 57% ± 3%*), *p<.05. The trend was similar but not statistically significant at 38.5°C. IL-6 release was decreased at 40°C at 24 hours in monocytes (cord 66% ± 15%; adult 74% ± 6%; p=NS) but not in macrophages (cord 94% ± 16%; adult 120% ± 18%, p=NS). Hypothermia: Culture at 32°C significantly decreased early (2 hr) release of TNF-α (23% ± 7%), IL-1β (49% ± 17%) and IL-6 (35% ± 12%) by adult monocytes and TNF-α (35% ± 4%) and IL-6 (36% ± 6%) by adult macrophages (all p<.01). By 24 hours there was no significant effect of hypothermia on cytokine release. Conclusions: Early release of cytokines was decreased by hypothermia but increased by hyperthermia. Prolonged hyperthermia had a differential effect, decreasing the proinflammatory cytokines TNF-α and IL-1β but not the counterregulatory cytokine IL-6. Further study of the effect of temperature on cytokine production may provide insight into beneficial or detrimental effects of alterations in body temperature during infection and other pathologic states.