Circadian characteristics of interleukin-6 in blood and urine of clinically healthy men.

The cytokine interleukin-6 (IL-6) is a multi-functional small peptide molecule that is produced by various types of lymphoid and non-lymphoid cells and plays a central role in hematopoiesis, host defense mechanisms, and acute phase reactions, including regulation of inflammatory and immune responses. A high-sensitivity ELISA assay was applied to serum (S) and urine (U) samples available from 10 men (median age = 50y, range = 46-71y) in order to compare circadian characteristics of IL-6 between assays and in 2 biological fluids. S and U samples were collected at 3-h intervals for 24hrs beginning at 19:00h on May 14, 1993 (8 samples/subj) and frozen at -25 degrees C until analysis. IL-6 in U was adjusted for time & volume (pg/hr) and assigned to midpoint of collection interval. A significant time-effect was found by ANOVA and a high-amplitude circadian rhythm was detected by the least-squares fit of a 24-hr &/or 24+12-hr cosine for each assay. Higher serum IL-6 values were detected throughout the night, with a peak at 01:00h, and lower values throughout the day, with a nadir at 10:00h. In contrast, IL-6 values in urine were highest during the day, with a major peak in the afternoon at 17:30h and a minor peak at 08:30h, and lowest values overnight, with a nadir at 23:30h. Of interest, the rhythm in urinary IL-6 concentration (pg/ml) was more prominent than hourly excretion rate (pg/hr). Thus, endogenous IL-6 (and possibly other cytokine) levels may be significantly influenced by their large and predictable day-night variations and the biological fluid used.

Circadian characteristics of circulating interleukin-6 in men.

BACKGROUND: The cytokine interleukin-6 (IL-6) is a multifunctional small-peptide molecule that is produced by various types of lymphoid and nonlymphoid cells. It plays a central role in hematopoiesis, host defense mechanisms, and acute-phase reactions, including regulation of inflammatory and immune responses. METHODS: Because a circadian time structure has been shown to characterize nearly every biologic function tested in human beings, including some cytokines, we sought to investigate the 24-hour pattern of circulating IL-6 in a group of 11 clinically symptom-free men (median age, 50 years; range, 46 to 72 years). Blood samples were obtained every 3 hours for 24 hours (eight samples per subject), and serum was frozen until analysis for IL-6 with a solid-phase ELISA. RESULTS: Average IL-6 values ranged from 1.66 to 5.38 pg/ml, with lowest to highest values within 24 hours ranging from 1.20 to 7.58 pg/ml (120% to 531%) between subjects. On average, values were greater than the mean throughout the night, with a peak at 01:00 hours and less than the mean throughout the day, with a nadir at 10:00 hours. A significant time effect was found by analysis of variance; and a high-amplitude circadian rhythm was described by the least-squares fit of a 24-hour cosine (p < 0.001; amplitude, 41% +/- 5%; acrophase, 02:16 +/- 00:28 hours). In addition, a positive correlation between mean IL-6 levels and age was found (r = 0.63, p = 0.037). CONCLUSIONS: Because monitoring of endogenous cytokine levels is suggested for assessing immune function and pathologic condition, clinical decisions and immunotherapies may be significantly influenced by the large and predictable day-night variations in endogenous cytokine production and bioactivity.

Analysis of elevated serum interleukin-6 levels in rheumatoid arthritis: correlation with erythrocyte sedimentation rate or C-reactive protein.

The purpose of this study was to determine whether selected antirheumatic drugs would suppress elevated circulating interleukin-6 (IL-6) levels in patients with rheumatoid arthritis (RA). The 267 patients who enrolled in a double-blind randomized protocol received placebo, naproxen (1500 mg/day), or prinomide (1500 mg/day) for up to 16 weeks. Serum samples from 143 of the patients completing the trial and from 135 normal donors were analyzed by quantitative sandwich enzyme-linked immunosorbent assay for IL-6 concentrations. A mean normal IL-6 value was determined to be 3 pg/ml (95th percentile value = 10 pg/ml). IL-6 levels at baseline for the patients with RA were significantly higher than those for control subjects (p < 0.0001). Elevated IL-6 levels (> 10 pg/ml) at baseline were found in 80% of subjects with RA (median = 36 pg/ml, range 12 to 403). For patients with elevated levels of either IL-6, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) at baseline, initial median values of IL-6, CRP, and ESR were compared with those from the final visit for each treatment group. There was no significant decrease in IL-6 levels with treatment. Median CRP levels decreased significantly, from 1.9 to 0.8 mg/dl (p = 0.002), as did median ESR (37 to 34 mm/hr, p = 0.013), only in the prinomide-treated group.

Handcuff neuropathy revisited.

Peripheral nerve injury due to handcuff placement has been reported in the past, always involving the superficial radial nerve, and sometimes involving other peripheral nerves at the wrist. We present two unusual cases in which the ulnar nerves were affected, but the radial nerves were normal or only minimally affected. This serves to emphasize a broader clinical spectrum of handcuff injury. Significant disability may result. These cases also involve alcohol intoxication, which may predispose patients to this type of injury because of overly aggressive application of restraints motivated by the patients' bellicose behavior.