Modulation of IL-6 production during the menstrual cycle in vivo and in vitro.

During the menstrual cycle (MC), premenopausal women experience changes in basal temperature and their physical condition and well-being. Premenopausal female patients with chronic inflammatory diseases demonstrate changes in disease activity during the MC. The study was initiated to explore reasons for these phenomena. The sex hormone-modulated lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) secretion in a whole blood assay, serum IL-6 concentration, and serum sex hormone concentrations were studied throughout the MC in five healthy female subjects (median, 28 years; mean, 31.2+/-2.2 years, 26-38 years). Serum IL-6 concentration demonstrated a significant increase in the luteal phase of the MC and was elevated when serum dehydroepiandrosterone (DHEA) was low and vice versa. DHEA decreased LPS-induced IL-6 secretion at six of seven time points during the MC (DHEA, p = .047). In contrast, beta-estradiol and testosterone increased LPS-induced IL-6 secretion in six of seven time points during the MC (significant for testosterone, p = .005). The study demonstrates oscillation of serum IL-6 concentration during the MC and the marked MC-dependent modulation of IL-6 secretion by sex hormones. These mechanisms may be involved in the changes in the basal temperature, the general condition, and, in patients with chronic inflammatory diseases, of disease activity during the MC.

Favorable role of interleukin 10 in patients with polymyalgia rheumatica.

OBJECTIVE: To determine the relationship between the antiinflammatory molecule interleukin 10 (IL-10) and disease symptoms, IL-1beta, tumor necrosis factor (TNF), and IL-1 receptor antagonist (IL-1ra) in patients with polymyalgia rheumatica (PMR). METHODS: In 102 patients with PMR, we determined the severity of the disease by the presence of typical clinical symptoms (symptom score with a maximum of 10 points). IL-10, IL-1beta, TNF, and IL-1ra were measured in all patients and 31 age matched healthy controls by enzyme immunometric assays. RESULTS: Compared to patients with elevated serum levels, patients with normal serum levels of IL-10 (below the mean + 3 SD of controls, 7.79 pg/ml) more often had adynamia (p = 0.045), bilateral muscular pain in shoulders, upper arms or neck (p = 0.045), bilateral muscular pain in the pelvic girdle (p < 0.001), headache (p = 0.014), morning stiffness (p < 0.001), symptoms of depression (p = 0.013), and initial weight loss (p = 0.011), and had a higher symptom score (5.5+/-0.4 vs 3.7+/-0.3; p < 0.001). The overall symptom score correlated negatively with IL-10 serum levels (Rrank = -0.421, p < 0.001). IL-10 correlated negatively with IL-1beta (p = 0.013) and TNF-alpha (p = 0.039). The association between elevated serum levels of IL-10 and low serum levels of IL-1beta and TNF was observed only in patients with corticosteroid treatment. In these patients, elevated serum levels of IL-10 were positively associated with an increased ratio of IL-1ra to IL-1beta. CONCLUSION: Elevated serum levels of IL-10 were associated with a more mild form of PMR. This study indicates a favorable role of IL-10 in patients with PMR.

Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence.

Interleukin-6 (IL-6) is one of the pathogenetic elements in inflammatory and age-related diseases such as rheumatoid arthritis, osteoporosis, atherosclerosis, and late-onset B cell neoplasia. In these diseases or during aging, the decrease in production of sex hormones such as dehydroepiandrosterone (DHEA) is thought to play an important role in IL-6-mediated pathogenetic effects in mice. In humans, we investigated the correlation of serum levels of DHEA, DHEA sulfate (DHEAS), or androstenedione (ASD) and IL-6, tumor necrosis factor-alpha, or IL-2 with age in 120 female and male healthy subjects (15-75 yr of age). Serum DHEA, DHEAS, and ASD levels significantly decreased with age (all P < 0.001), whereas serum IL-6 levels significantly increased with age (P < 0.001). DHEA/DHEAS and IL-6 (but not tumor necrosis factor-alpha or IL-2) were inversely correlated (all patients: r = -0.242/-0.312; P = 0.010/0.001). In female and male subjects, DHEA and ASD concentration dependently inhibited IL-6 production from peripheral blood mononuclear cells (P = 0.001). The concentration-response curve for DHEA was U shaped (maximal effective concentration, 1-5 x 10(-8) mol/L), which may be the optimal range for immunomodulation. In summary, the data indicate a functional link between DHEA or ASD and IL-6. It is concluded that the increase in IL-6 production during the process of aging might be due to diminished DHEA and ASD secretion. Immunosenescence may be directly related to endocrinosenescence, which, in turn, may be a significant cofactor for the manifestation of inflammatory and age-related diseases.