Variability in body temperature in healthy adults and in patients receiving chemotherapy: prospective observational cohort study.

Between-individual variability of body temperature has been little investigated, but is of clinical importance: for example, in detection of neutropenic sepsis during chemotherapy. We studied within-person and between-person variability in temperature in healthy adults and those receiving chemotherapy using a prospective observational design involving 29 healthy participants and 23 patients undergoing chemotherapy. Primary outcome was oral temperature. We calculated each patient's mean temperature, standard deviation within each patient (within-person variability), and between patients (between-person variability). Secondary analysis explored temperature changes in the three days before admission for neutropenic sepsis. 1,755 temperature readings were returned by healthy participants and 1,765 by chemotherapy patients. Mean participant temperature was 36.16 C (95% CI 36.07-36.26) in healthy participants and 36.32 C (95% CI 36.18-36.46) in chemotherapy patients. Healthy participant within-person variability was 0.40 C (95% CI 0.36-0.44) and between-person variability was 0.26 C (95% CI 0.16-0.35). Chemotherapy patient within-person variability was 0.39 C (95% CI 0.34-0.44) and between-person variability was 0.34 C (95% CI 0.26-0.48). Thus, use of a population mean rather than personalised baselines is probably sufficient for most clinical purposes as between-person variability is not large compared to within-person variability. Standardised guidance and provision of thermometers to patients might help to improve recording and guide management.

Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats.

Febrile responses to bacterial pathogens are attenuated near term of pregnancy in several mammalian species. It is unknown, however, whether this reflects a fundamental physiological adaptation of female rats or whether it is specific to pregnancy. The aims of this study therefore were 1) to determine whether febrile responses to the bacterial endotoxin lipopolysaccharide (LPS) are attenuated in female vs. male rats and, if so, to identify possible mechanisms involved in modulating this and 2) to assess whether plasma concentrations of the anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), an important regulator of fever, are dependent on the physiological state of the female and could therefore be involved in modulating febrile responses. We found febrile responses were attenuated in cycling female vs. male rats and also in near-term pregnant dams vs. cycling females after intraperitoneal injection of LPS (0.05 mg/kg). Plasma levels of IL-1ra were significantly greater in female rats after injection of LPS, particularly during pregnancy, than in males. This was accompanied by attenuated levels of hypothalamic IL-1beta and cyclooxygenase-2 mRNA, two key mediators of the febrile response, in female rats. Furthermore, increasing plasma levels of IL-1ra in male rats by intraperitoneal administration of the recombinant antagonist attenuated hypothalamic mRNA levels of these mediators after LPS. These data suggest that there is a fundamental difference in febrile response to LPS between the genders that is likely regulated by IL-1ra. This may be an important mechanism that protects the developing fetus from potentially deleterious consequences of maternal fever during pregnancy.

The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia.

Maternal infections with bacterial or viral agents during pregnancy are associated with an increased incidence of schizophrenia in the offspring at adulthood although little is known about the mechanism by which maternal infection might affect fetal neurodevelopment. Exposure of pregnant rodents to the bacterial endotoxin, lipopolysaccharide (LPS), results in behavioral deficits in the adult offspring that are relevant to schizophrenia. It is however unknown whether these effects are due to the direct action of the inflammatory stimulus on the developing fetus, or due to secondary immune mediators (cytokines) activated at maternal/fetal sites. In this study we sought to elucidate the site of action of LPS, following a single intraperitoneal (i.p.) injection, in pregnant rats at gestation day 18. Animals received 5 muCi of iodinated LPS ((125)I-LPS) and its distribution was assessed in maternal/fetal tissues (1-8 h). In addition, induction of the inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, was measured in maternal/fetal tissues following maternal LPS challenge (0.05 mg/kg, i.p.) (2-8 h). (125)I-LPS was detected in maternal tissues and placenta, but not the fetus. This distribution was accompanied by significant increases in TNF-alpha, IL-1beta and IL-6 in maternal plasma and placenta, but not in fetal liver or brain. A significant increase in IL-1beta was however detected in fetal plasma, possibly due to transfer from the maternal circulation or placenta. Collectively, these data suggest that effects of maternal LPS exposure on the developing fetal brain are not mediated by the direct action of LPS, but via indirect actions at the level of the maternal circulation or placenta.