The time the participants required to finish the Grooved Pegboard test with the dominant hand served as an indication of fine motor control . Working memory was assessed with selleckbio the digit span forward and backward subtests of the Dutch translations of the Wechsler Adult Intelligence Scale (WAIS) III . The total number of correct responses on the two-second stimulus interval condition of the Paced Auditory Serial Addition Test (PASAT) served as a measure for divided attention under time pressure . The total number of correct responses on the Digit Symbol Test (SDT) of the WAIS III was chosen as an indication of psychomotor speed capacity as well as the information processing ability . Reading speed, colour naming speed and distractibility were measured with the Stroop colour-word naming test  (Pearson Assessment and Inofrmation BV, Amsterdam, The Netherlands).
To measure a possible practice effect Mercaptopurine (6-MP) as a result of test-retesting of the CFTs, the same CFTs under the same conditions and time intervals were performed in a reference group of 10 healthy male volunteers that did not receive LPS.Data analysis and statisticsAll data were analyzed using SPSS version 16.01 (SPSS, Chicago, Illinois, USA). Results are expressed by means �� standard error of the mean or median (interquartile range (IQR)) depending on their distribution. LPS-induced effects were tested for significance with Friedman's analysis of variance (non-parametric test). To detect practice effect we compared the experimental group and the reference group with the repeated measurement-analysis of variance.
Correlation analysis was performed with the Spearman's correlation coefficient. Because of the exploratory nature of this study, a correction for multiple testing was not included. Statistical significance was defined as a P value less than 0.05.ResultsBaseline characteristicsBaseline characteristics of the 15 healthy male volunteers are shown next in Table ?Table1.1. All participants had a mean age of 23 �� 2 years, and had a high (college or university) educational level.Table 1Baseline demographic characteristics of the study groupLPS-induced changes in clinical and inflammatory parameters and cortisol levelsLPS administration induced the expected transient flu-like symptoms. Body temperature increased by 1.4 �� 0.1��C (P < 0.0001) and heart rate by 27 �� 2 bpm (P < 0.
0001). Cumulative symptom scores increased from a median score of 0 (IQR 0 to 1) to 4 (IQR 2 to 7) at 70 minutes after LPS administration, after which there was a decrease to a median of 2 (IQR 1 to 5) and 1 (IQR 0 to 2) at two and four hours, respectively (P < 0.0001). Relevant to the present study, LPS administration induced an increase in headache score from 0 score to a maximum of 2 (IQR 1 to 3) at 90 minutes after endotoxin administration (P < 0.0001).All plasma cytokine concentrations increased significantly (all P < 0.0001) after the administration of LPS (Figure ?(Figure1).1). Cortisol levels increased significantly from 0.31 �� 0.07 to 0.60 �� 0.07 ��mol/l (P < 0.0001) two hours after LPS administration and dropped to baseline levels eight hours after LPS administration (Figure ?(Figure11).
Figure 1LPS-induced changes in cytokine plasma concentrations, cortisol and brain specific proteins. Time -0- reflects baseline concentrations. Administration of lipopolysaccharide (LPS) resulted in a marked increase in TNF-��, IL-6, IL-10, IL-1Ra and ...LPS-induced changes in brain specific proteinsAs illustrated in Figure ?Figure1,1, NSE levels showed a small, but statistically significant decrease from 11.1 �� 0.47 to 7.7 �� 0.39 ��g/L after the administration of LPS (P < 0.0001).