Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of an onchocercal chorioretinopathy from the first detectable signs to a full blown oncho fundus is not fully understood. We investigated the intraocular humoral immune response against Onchocerca volvulus, human S-antigen, IRBP and crude retinal extract (using an ELISA) by examining paired aqueous humour and serum samples obtained from onchocerciasis patients (without [n = 10] and with ocular symptoms [n = 8]) and endemic controls [n = 14] from Sierra Leone (West Africa). A local intraocular anti-retinal IgG antibody production could not be demonstrated in onchocerciasis patients, whether they had ocular symptoms or not. A significantly higher level of O. volvulus antibodies and IgG was measured in the aqueous of onchocerciasis patients with ocular involvement, as compared to patients without ocular symptoms (Mann-Whitney ranksum test; p less than 0.001 and p less than 0.02 respectively). Since interleukin-6 (IL-6) plays an essential role in the differentiation of B cells into immunoglobulin producing plasma cells, we therefore measured this cytokine in paired aqueous and serum samples. Elevated IL-6 levels were found in the aqueous of two out of eight onchocerciasis patients tested. In view of these findings it seems improbable that retinal autoimmunity is a major factor in the pathogenesis of onchocercal chorioretinopathy. The high intraocular levels of antibodies against the parasite suggest a direct involvement of the parasite in the pathogenesis of onchocercal chorioretinopathy.
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PMID:Analysis of aqueous humour in ocular onchocerciasis. 203 8

Ivermectin treatment of onchocerciasis can induce adverse reactions. Mechanisms underlying these reactions are poorly understood but may include activation of neutrophils. This study investigated the acute-phase response in onchocerciasis patients during 2 days after ivermectin treatment. The acute-phase protein C-reactive protein (CRP) and cytokines that mediate the acute-phase response (tumor necrosis factor-alpha [TNF alpha] and interleukin-6 [IL-6]) were measured in 144 skin snip-positive onchocerciasis patients and 12 skin snip-negative controls who received one dose of ivermectin (150 micrograms/kg). No elevated TNF alpha levels were found, but IL-6 and CRP were elevated in 25.7% and 50.7% of the patients, respectively, after ivermectin treatment. Most patients (89.2%) with raised IL-6 also had raised CRP. Such increases were not observed in controls and in patients were correlated with adverse reactions and microfilarial densities. These findings suggest a possible role of the acute-phase response in microfilarial destruction following ivermectin treatment.
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PMID:C-reactive protein and interleukin-6 are elevated in onchocerciasis patients after ivermectin treatment. 807 26

Adverse reactions following treatment of onchocerciasis and bancroftian filariasis are common and frequently severe. They are generally caused not by direct drug toxicity but by host inflammatory responses to dying microfilariae. To define the responsible mechanism, serial blood levels of interleukin-6 (IL-6) and tumor necrosis factor (TNF) were studied in 15 microfilaria-positive patients (10 with bancroftian filariasis, 5 with onchocerciasis) and 4 microfilaria-negative persons after diethylcarbamazine treatment. Elevations in IL-6 correlated with the occurrence and severity of clinical symptoms after treatment; for the onchocerciasis patients IL-6 levels directly reflected pretreatment intensity of infection. Serum TNF levels also rose but did not correlate directly with infection intensity or reaction severity. Microfilaria-negative controls remained asymptomatic with no significant rise in either cytokine. These findings suggest an etiologic role for systemically elevated cytokines in the inflammatory reactions developing after treatment of filarial infections in humans.
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PMID:Interleukin-6 and tumor necrosis factor in the pathogenesis of adverse reactions after treatment of lymphatic filariasis and onchocerciasis. 816 93

Suramin is a symmetric polysulfonated naphthylamine-benzamide urea derivative approved for the treatment of trypanosomiasis and onchocerciasis and a known P2 (ATP/UTP purine receptor) antagonist. Here, we report its ability to inhibit the important CD40-CD154 costi-mulatory interaction required for T cell activation and the development of an effective immune response. In vitro, it inhibited the binding of both human and murine CD154 (CD40L) to their receptor (CD40) even in the presence of protein-containing media and prevented the CD154-induced proliferation of human B cells as well as the corresponding increase in surface expression of CD86, CD80, CD40, and MHC class II in a concentration-dependent manner. Furthermore, in isolated human islets, it also decreased the CD154-induced release of inflammatory cytokines such as IFN-g, interleukin-6 (IL-6), and IL-8. Suramin was selected for investigation because it has been reported to be an inhibitor of the interaction of TNF-a with its receptor and CD154 is a member of the TNF-family. However, it turned out to be a considerably, about 30-fold, more effective inhibitor of the CD40-CD154 protein-protein interaction than of the corresponding TNF interaction. Its median inhibitory concentration (IC50 50 mM) is somewhat higher than for the P2-receptor, but well within the range of its therapeutic concentration levels. Suramin shows considerable polypharmacology, but its interference with the positive costimulatory interaction might provide a possible, not yet identified mechanism for its ability to suppress T cell activity and induce immunosuppression, which might also have limited its clinical usefulness in the treatment of AIDS and cancer.
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PMID:Suramin inhibits the CD40-CD154 costimulatory interaction: a possible mechanism for immunosuppressive effects. 1928 94

Negative emotions are reliably associated with poorer health (e.g., Kiecolt-Glaser, McGuire, Robles, & Glaser, 2002), but only recently has research begun to acknowledge the important role of positive emotions for our physical health (Fredrickson, 2003). We examine the link between dispositional positive affect and one potential biological pathway between positive emotions and health-proinflammatory cytokines, specifically levels of interleukin-6 (IL-6). We hypothesized that greater trait positive affect would be associated with lower levels of IL-6 in a healthy sample. We found support for this hypothesis across two studies. We also explored the relationship between discrete positive emotions and IL-6 levels, finding that awe, measured in two different ways, was the strongest predictor of lower levels of proinflammatory cytokines. These effects held when controlling for relevant personality and health variables. This work suggests a potential biological pathway between positive emotions and health through proinflammatory cytokines.
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PMID:Positive affect and markers of inflammation: discrete positive emotions predict lower levels of inflammatory cytokines. 2560 33