Production of Interleukin-6 Over a Hyperthermic Range by Lipopolysaccharide-Stimulated Neutrophils

摘要

Neutrophils are an essential cell of the immune system, responsible for phagocytosis of bacterial pathogens. The neutrophil response to and production of cytokines is paramount to successful immune responses. Interleukin-6 (IL-6) is an important cytokine produced by the neutrophil. This cytokine has pleotropic activity but of interest in this study is its ability to act as an endogenous pyrogen and cause fever. It was wondered what the effect of elevated temperature would have on the neutrophil production of IL-6. It was hypothesized that elevated temperature would decreased the amount of neutrophil produced IL-6. Neutrophils were isolated by density gradient centrifugation then standardized to 1,000,000 per mililiter in cell culture fluid. The cells were primed with FMLP and subsequently stimulated with the bacterial endotoxin, lipopolysaccharide (LPS) serotype 0111:B4. To mimic the conditions of fever, the cells were incubated at various temperatures representing a range from normal to severe fever. Samples of culture supernatant were pulled at various time intervals and later assayed for IL-6 levels. The results reveal that LPS stimulated neutrophils produced picogram quantities of IL-6. The results among three batches were highly variable but noticeable trends were present. On average, normal body temperature (37 deg C) levels of IL-6 were more than either 38.5 deg C or 40 deg C. However at 41 deg C, levels of IL-6 were much higher than base line. This suggests that during mild and moderate fever IL-6 levels may be slightly depressed, but are enhanced at the upper end of the physiological range.