Assessment Of Tumour Necrosis Factor-Alpha (Tnf- Α) And Creatinine Levels In Echis Ocellatus Bite Victims In Jos Metropolis, Nigeria

This study was designed to assess tumour necrosis factor-alpha and creatinine levels in Echis ocellatus bite victims. A total of 50 subjects were recruited. Out of this number, 40 were victims of E. ocellatus bite and the remaining 10 were non-victims of snake bite who served as the control group. Blood samples were collected from the victims within 24 hours of the snake bite and EchiTAb-G antivenom administered within the same period. Another batch of blood sample was collected 48 hours post-administration of the anti-venom. Tumour necrosis factor-alpha (TNF-alpha) levels were estimated by the Enzyme Linked Immunosorbent Assay technique while creatinine levels were determined using kinetic-spectrophotometric procedure. The mean serum levels of tumour necrosis factor-alpha and creatinine were significantly increased in E. ocellatus bite victims compared with the control group (P<0.05). Furthermore, the mean serum level of TNFalpha was significantly lower in E. ocellatus bite victims, post-administration of anti-venom, compared with the pre-administration of anti-venom (P<0.05). In contrast, no significant difference was observed in the mean serum level of creatinine in E. ocellatus bite victims, post-administration of anti-venom, compared with the pre-administration of anti-venom (P>0.05). Moreover, the mean serum level of creatinine was found to be significantly increased in E. ocellatus bite victims, post-administration of anti-venom, compared with the control group (P<0.05), while no significant difference was observed in the mean serum level of tumour necrosis factor-alpha in E. ocellatus bite victims, post-administration of anti-venom, compared with the control group(P>0.05). A positive correlation existed between tumour necrosis factor-alpha and creatinine levels in E. ocellatus bite subjects (r= 0.782). Echis ocellatus bite is a risk factor for renal damage indicated by an elevated serum creatinine, thus health authorities should make EchiTAb-G anti-venom freely available in health facilities and administered as quickly as possible to reduce the risk of renal damage in Echis ocellatus bite-prone areas

Possible Role of Interleukin-6 in Rheumatoid Arthritis

Background: Rheumatoid Arthritis (RA) is an autoimmune disease. Many etiological agents are proposed to play a role in its pathogenecity. One of these factors is cytokines such as Interleukin6. Material & Methods: ELISA method has been used for IL-6 estimation in 75 RA patients in comparison with 61 SLE as patient controls and 39 apparently healthy controls. Results: This study showed that there was an elevation of IL-6 in the sera of RA patients with high significant differences between RA patients and controls (P< 0.001). Moreover a good correlation between IL-6 level & RF titer were observed. However, for most patients with high IL-6 were shown to be HLA-DR4. Conclusions: Interleukin-6 play a crucial role in the disease which may be participate in the severity of RA & subsequently its treatment

Evaluation of Leptin, LIF and IL-6 Serum Levels in Lymphoid Leukemia Patients

Background & Objectives: Leptin is a hormone secreted from adipocyte tissue with established role in the differentiation and proliferation of hematopoietic cells. This hormone has major impact on fat metabolism. LIF is a pleiotropic cytokine with extensive hematopoietic, neuronal, and endocrine actions. LIF and IL-6 are leading to decreased level of leptin by activating signaling via their own receptors. Body mass index (BMI) has a direct connection with the leptin. It seems that Hb and HCT levels are also implicated in disease prognosis. This study was conducted to evaluate leptin, LIF and IL-6 serum levels and also to measure the amounts of BMI, Hb and HCT in lymphoid leukemia patients. Methods: The study was carried out on 30 leukemia patients (15 cases ALL and 15 cases CLL). Fifteen healthy subjects were considered as control. Serum levels of leptin, LIF and IL-6 were measured by ELISA. BMI was calculated by statistical formula. The amount of Hb and HCT were measured by cell counter. Data was analyzed by SPSS software. Statistical differences between groups were assessed by t test, and p <0.05 was considered significant. Results: Leptin serum level showed a decrease in ALL patients (p <0.002), but there was an increase in CLL patients when comparing with control group (p <0.003). BMI and serum levels of leptin, LIF and IL-6 were showed a significant decrease in ALL patients in comparison with control group (p <0.05). Although, LIF serum levels and BMI in CLL patients showed a decrease, a significant increase in leptin serum level was observed (p <0.05). A decrease in IL-6 level was also observed which was not significant. The relation between BMI and leptin serum level in ALL and CLL patients were not significant, nevertheless it was significant in control group (p <0.05). Hb and HCT levels in both ALL and CLL patients showed a significant decrease (p <0.05). Conclusion: Findings on serum levels of LIF, IL-6, Leptin, Hb and HCT and also its relations with BMI in ALL and CLL patients suggest that, these factors may have important role in physiopathology of lymphoid leukemia

Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor

RA is a chronic, debilitating disease in which articular inflammation and joint destruction are accompanied by systemic manifestations including anaemia, fatigue and osteoporosis. IL-6 is expressed abundantly in the SF of RA patients and is thought to mediate many of the local and systemic effects of this disease. Unlike a number of other cytokines, IL-6 can activate cells through both membrane-bound (IL-6R) and soluble receptors (sIL-6R), thus widening the number of cell types responsive to this cytokine. Indeed, trans-signalling, where IL-6 binds to the sIL-6R, homodimerizes with glycoprotein 130 subunits and induces signal transduction, has been found to play a key role in acute and chronic inflammation. Elevated levels of IL-6 and sIL-6R in the SF of RA patients can increase the risk of joint destruction and, at the joint level, IL-6/sIL-6R can stimulate pannus development through increased VEGF expression and increase bone resorption as a result of osteoclastogenesis. Systemic effects of IL-6, albeit through conventional or trans-signalling, include regulation of acute-phase protein synthesis, as well as hepcidin production and stimulation of the hypothalamo-pituitary-adrenal axis, the latter two actions potentially leading to anaemia and fatigue, respectively. This review aims to provide an insight into the biological effects of IL-6 in RA, examining how IL-6 can induce the articular and systemic effects of this diseas

Circulating levels of ciliary neurotrophic factor in normal pregnancy and preeclampsia

Ciliary neurotrophic factor (CNTF) has been shown to decrease food intake in mouse models of obesity and to improve insulin sensitivity. It is well known that tight regulation of glucose metabolism is essential for successful gestational outcomes (e.g. fetal growth), and that abnormal insulin resistance is associated with preeclampsia (PE). To investigate the possibility that CNTF might be involved in the regulation of insulin resistance during pregnancy, circulating levels of CNTF were assessed in non-pregnant, normal pregnant, postpartum, and pregnant women with PE. Sera from healthy non-pregnant women (n10), pregnant women (n30:1st trimester;n10, 2nd trimester n10;3rd trimester;n10), postpartum women (n10), and patients with PE (n11) were studied with Western blotting. Circulating CNTF was detected by Western blotting, and the levels of CNTF in pregnant women were decreased as compared with those in non-pregnant women, and tended to decrease as pregnancy progressed. A significant decrease was found in PE as compared with normal pregnancy. Circulating CNTF might be associated with physiological and abnormal insulin resistance during pregnancy.</p

Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor

RA is a chronic, debilitating disease in which articular inflammation and joint destruction are accompanied by systemic manifestations including anaemia, fatigue and osteoporosis. IL-6 is expressed abundantly in the SF of RA patients and is thought to mediate many of the local and systemic effects of this disease. Unlike a number of other cytokines, IL-6 can activate cells through both membrane-bound (IL-6R) and soluble receptors (sIL-6R), thus widening the number of cell types responsive to this cytokine. Indeed, trans-signalling, where IL-6 binds to the sIL-6R, homodimerizes with glycoprotein 130 subunits and induces signal transduction, has been found to play a key role in acute and chronic inflammation. Elevated levels of IL-6 and sIL-6R in the SF of RA patients can increase the risk of joint destruction and, at the joint level, IL-6/sIL-6R can stimulate pannus development through increased VEGF expression and increase bone resorption as a result of osteoclastogenesis. Systemic effects of IL-6, albeit through conventional or trans-signalling, include regulation of acute-phase protein synthesis, as well as hepcidin production and stimulation of the hypothalamo-pituitary-adrenal axis, the latter two actions potentially leading to anaemia and fatigue, respectively. This review aims to provide an insight into the biological effects of IL-6 in RA, examining how IL-6 can induce the articular and systemic effects of this disease

IL6/sIL6R Regulates TNFα-Inflammatory Response in Synovial Fibroblasts Through Modulation of Transcriptional and Post-Transcriptional Mechanisms

[Abstract] Introduction: The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods: SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value < 0.05 was considered statistically significant. Results: The stimulation of SF with IL6/sIL6R and TNFα, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6/sIL6R. Furthermore, we also demonstrate that TNFα and IL6/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK/STAT pathways. Conclusions: These results point out to a highly orchestrated response to IL6 in TNFα-induced SF and provide additional insights into the role of IL6/sIL6R in the context of RA, highlighting the contribution of IL6/sIL6R to the interplay of SF with other inflammatory cells.Instituto de Salud Carlos III; FIS 16/00032Instituto de Salud Carlos III; RETICS RD16/0012 RIE

Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor

RA is a chronic, debilitating disease in which articular inflammation and joint destruction are accompanied by systemic manifestations including anaemia, fatigue and osteoporosis. IL-6 is expressed abundantly in the SF of RA patients and is thought to mediate many of the local and systemic effects of this disease. Unlike a number of other cytokines, IL-6 can activate cells through both membrane-bound (IL-6R) and soluble receptors (sIL-6R), thus widening the number of cell types responsive to this cytokine. Indeed, trans-signalling, where IL-6 binds to the sIL-6R, homodimerizes with glycoprotein 130 subunits and induces signal transduction, has been found to play a key role in acute and chronic inflammation. Elevated levels of IL-6 and sIL-6R in the SF of RA patients can increase the risk of joint destruction and, at the joint level, IL-6/sIL-6R can stimulate pannus development through increased VEGF expression and increase bone resorption as a result of osteoclastogenesis. Systemic effects of IL-6, albeit through conventional or trans-signalling, include regulation of acute-phase protein synthesis, as well as hepcidin production and stimulation of the hypothalamo-pituitary-adrenal axis, the latter two actions potentially leading to anaemia and fatigue, respectively. This review aims to provide an insight into the biological effects of IL-6 in RA, examining how IL-6 can induce the articular and systemic effects of this diseas

Melittin induces in vitro death of Leishmania (Leishmania) infantum by triggering the cellular innate immune response

Abstract\ud \ud Background\ud \ud Apis mellifera venom, which has already been recommended as an alternative anti-inflammatory treatment, may be also considered an important source of candidate molecules for biotechnological and biomedical uses, such as the treatment of parasitic diseases.\ud \ud \ud Methods\ud Africanized honeybee venom from Apis mellifera was fractionated by RP-C18-HPLC and the obtained melittin was incubated with promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Cytotoxicity to mice peritoneal macrophages was evaluated through mitochondrial oxidative activity. The production of anti- and pro-inflammatory cytokines, NO and H2O2 by macrophages was determined.\ud \ud \ud Results\ud Promastigotes and intracellular amastigotes were susceptible to melittin (IC50 28.3 μg.mL−1 and 1.4 μg.mL−1, respectively), but also showed mammalian cell cytotoxicity with an IC50 value of 5.7 μg.mL−1. Uninfected macrophages treated with melittin increased the production of IL-10, TNF-α, NO and H2O2. Infected melittin-treated macrophages increased IL-12 production, but decreased the levels of IL-10, TNF-α, NO and H2O2.\ud \ud \ud Conclusions\ud The results showed that melittin acts in vitro against promastigotes and intracellular amastigotes of Leishmania (L.) infantum. Furthermore, they can act indirectly on intracellular amastigotes through a macrophage immunomodulatory effect.The authors would like to thank the State of São Paulo Research\ud Foundation (FAPESP, proc. n. 2011/23236-4 and n. 2009/53846-9), the National Council for Scientific and Technological Development (CNPq, proc. n. 563582/2010-3), the Coordination for the Improvement of Higher Education Personnel (CAPES, AUXPE Toxinologia 1219/2011, proc. n. 23038.000823/2011-21 and AUXPE proc. n. 23038.005536/2012-31) and FINEP (protocol number 01.12.0450.01). DCP (306066/2011-4), RSFJr and AGT are CNPq research fellows