Including Interleukin-6 Levels Research Articles

Estrogen replacement therapy modulation of the insulin-like growth factor system in monkey knee joints.

Epidemiologic studies have suggested that estrogen replacement therapy may lower the risk of osteoarthritis in women, but the mechanism of this effect is unknown. Since estrogen acts in other tissues in part through regulation of the insulin-like growth factor (IGF) system as well as cytokines including interleukin-6 (IL-6), we determined whether estrogen replacement regulates the levels of these factors in synovial fluid (SF). Levels of IGF-1, IGF-2, IGF binding proteins (IGFBP) 1-3, and IL-6 were measured in SF samples obtained from 67 female adult cynomolgus monkeys that had been ovariectomized and treated for 30 months in 1 of 3 groups. Group 1 (n = 24) had no estrogen replacement (control), group 2 (n = 22) received estrogen (Premarin) at the human equivalent of 0.625 mg/day, and group 3 (n = 21) received estrogen at the same dose as group 2, plus progesterone (Provera) at the equivalent of 2.5 mg/day. Compared with controls, estrogen-treated monkeys had 2-fold higher SF levels of IGF-1 (P < 0.001), 1.7-fold higher IGF-2 (P < 0.006), 5.9-fold higher IGFBP-1 (P < 0.02), and 2.5-fold higher IGFBP-3 (P < 0.001). Estrogen plus progesterone-treated monkeys had SF levels of IGF-1, IGF-2, IGFBP-1, and IGFBP-3 that were intermediate between the levels in the control and estrogen groups, except that the level of IGFBP-3 was significantly greater than that in the control group (P < 0.001). SF levels of IGFBP-2 and IL-6 did not differ by treatment group. Treatment group did not affect the serum levels of IGF-1 and IL-6, but IGF-2 and IGFBP-3 were increased by 1.6- and 1.8-fold, respectively, in the estrogen group (P < 0.001). There was no correlation between changes in serum and SF levels of IGF components, except for a weak correlation for IGFBP-3 levels from control (r = 0.464, P = 0.04) and estrogen-treated (r = 0.577, P = 0.008) animals. This study demonstrates a significant effect of estrogen replacement on IGF system components in synovial fluid, of which at least some are distinct from any systemic changes observed. The results indicate a potential stimulatory effect of estrogen on joint tissues in vivo.

Elevation of plasma interleukin-6 level is involved in postoperative fever following major oral and maxillofacial surgery

Objective. The purpose of this study was to evaluate whether the changes in plasma cytokine levels including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) are involved in postoperative fever following oral and maxillofacial surgery. Study design. Ten patients undergoing elective oral and maxillofacial surgery were studied. We investigated the plasma cytokine levels by using an enzyme-linked immunosorbent assay and measured the core temperature and degree of postoperative shivering and peripheral vasoconstriction after surgery. The relationships between the changes in plasma cytokine levels and postoperative fever were statistically evaluated using Spearman's rank correlation coefficients. Results. The elevation of plasma IL-6 level was significantly correlated with the increase in core temperature after surgery and with the degree of postoperative shivering and vasoconstriction, whereas the changes in plasma IL-1β or TNF-α levels were not. Conclusions. Elevation of plasma IL-6 level is probably involved in postoperative fever following oral and maxillofacial surgery.

Does the duration of cardiopulmonary bypass or aortic cross-clamp, in the absence of blood and/or blood product administration, influence the IL-6 response to cardiac surgery?

Cardiopulmonary bypass (CPB) induces a systemic inflammatory response characterized by release of proinflammatory cytokines, including interleukin 6 (IL-6). Recent reports suggest that plasma IL-6 is increased after CPB. Previous studies evaluating the influence of duration of CPB and/or aortic cross-clamp time on the release of IL-6 are conflicting. Infusion of blood and blood products during these studies may have influenced plasma concentrations of proinflammatory cytokines by inducing host cell (monocyte) activation and IL-6 release. The purpose of our investigation was to determine, in an environment free from blood and/or blood product administration, the influence of duration of CPB and/or aortic cross-clamp on the magnitude of the IL-6 response in patients undergoing cardiac surgery. We prospectively evaluated plasma IL-6 levels preinduction (T0) and at sternal closure in 16 patients undergoing CPB (coronary artery bypass grafting, n = 9; valvular cardiac surgery, n = 7) to determine whether there is a correlation between the absolute increase in IL-6 and the duration of CPB or aortic cross-clamp time. None of the patients received blood and/or blood products during the study to control for the introduction of additional activated cells and soluble mediators, including IL-6. The results demonstrate that the magnitude of the IL-6 response to CPB is positively correlated with the duration of CPB but not with duration of aortic cross-clamp. It seems that induction of IL-6 release is part of a normal response to CPB and does not depend on activation of host cells during prolonged aortic cross-clamp. The activation or presence of inflammatory cytokines associated with administration of blood and/or blood products could have influenced previously published investigations relating the influence of duration of CPB and/or aortic cross-clamp time to the magnitude of the IL-6 response. This study found a positive correlation between the magnitude of the interleukin 6 response to cardiopulmonary bypass and duration of cardiopulmonary bypass (but not duration of aortic cross-clamp) when measurements were made in the absence of blood/blood product transfusion. Future studies evaluating strategies to reduce cytokine responses to cardiopulmonary bypass should therefore control for cardiopulmonary bypass duration.

Interleukin 6 and AIDS-associated Kaposi's sarcoma: a nested case control study within the Multicenter AIDS Cohort Study.

Since the beginning of the AIDS epidemic, there has been considerable research on the etiology of Kaposi's sarcoma (KS) among HIV-infected individuals. A number of studies have confirmed that HIV or HIV-encoded products can interact with human cells to induce the production of cytokines, including interleukin 6 (IL-6). In vitro observations have indicated that AIDS-KS cells can produce significant levels of IL-6 and also respond to this cytokine. Preliminary data suggested that IL-6 may be elevated among HIV-infected individuals that subsequently develop AIDS-KS. The objective of this study was to determine if elevated levels of IL-6 are associated with an increased incidence of AIDS-KS compared to other AIDS-defining illnesses such as opportunistic infections (OIs). Serum IL-6 levels were determined by ELISA in frozen sera collected from participants in the Multicenter AIDS Cohort Study (MACS) at 6 months prior to AIDS diagnosis, in 73 cases (AIDS-KS), and 152 controls (OI). Elevated IL-6 levels were more prevalent among men with AIDS-OI than those with AIDS-KS: crude odds ratio (OR), 0.4 (95% CI, 0.2-0.9). Models of multivariate logistic regression were used to study potential confounders. Sexual behavior variables did not seem to confound the association between IL-6 and AIDS-KS. The higher prevalence of IL-6 among controls could be explained by the association of higher levels of IL-6 with lower levels of CD4 T cell number. IL-6 may be a marker of severe immune dysfunction among HIV-infected individuals.

Melanoma-Derived Interleukin 6 Inhibits In Vivo Melanoma Growth

Malignant melanomas are capable of producing a wide range of cytokines with multiple biologic functions, including interleukin 6 (IL-6). We have observed an inverse relationship between IL-6 production of three B16-derived murine melanoma cell lines (NP133, HFH18, and HFH(M)) and the tumorigenicity of these melanoma cells in syngeneic mice. To further test the effect of IL-6 on melanoma growth, a non-IL-6-producing murine B16-derived melanoma cell line (HFH18) was transfected with a murine IL-6 expression vector, resulting in stable transfectants (HFH18/IL-6(+)) that expressed significant amounts of IL-6 mRNA and secreted high levels of bioactive IL-6. Syngeneic C57BL/6 mice inoculated subcutaneously with HFH18/IL-6(+) cells developed tumors that reached a final mean diameter of less than half the size of tumors that developed in mice inoculated with either HFH18 parental or HFH18 cells transfected with the IL-6 cDNA in the non-coding 3'-5' orientation (HFH18/IL-6(-) cells). In addition, mice bearing IL-6-producing HFH18/IL-6(+) tumors survived twice as long as mice bearing HFH18 parental or HFH18/IL-6(-) tumors. The specificity of melanoma growth inhibition by IL-6 was confirmed by the reversal of the slow-growing phenotype of HFH18/IL-6(+) cells by local peritumoral administration of neutralizing alpha-murine IL-6 antibody. IL-6-producing melanoma cells exerted a growth-inhibitory effect on distant parental tumors in a dose-dependent manner. The growth of HFH18/IL-6(+) melanomas was also decreased in nude mice, suggesting that melanoma-derived IL-6 may mediate this anti-tumor effect independently of a normal host B- and T-cell immune response. Thus, melanoma-derived IL-6 exerts a significant inhibitory effect on cutaneous melanoma growth and progression. These results indicate that melanoma cytokines may have a profound effect on tumor pathogenesis.

Cytokines predict coronary aneurysm formation in Kawasaki disease patients

In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor alpha (TNF-alpha) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL-6, IL-8, sIL-2R and TNF alpha were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNF alpha. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P < 0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P < 0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNF alpha were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNF alpha were significantly higher in the patients with than in those without coronary aneurysm (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)