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

Bacterial infections in the immunocompromized host cause considerable mortality, and even the recently developed antimicrobial strategies often fail to cure these infections, especially in granulocytopenic patients. Cytokines and hematopoietic growth factors have been shown to stimulate host defense mechanisms in vitro and in vivo. We discuss the possible role of the pro-inflammatory cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 as modulators of host resistance to bacterial infections. Interleukin-1 has been shown effective in various animal models of potentially lethal bacterial infection, even during severe granulocytopenia. The protective mechanism of interleukin-1 may be mediated via downregulation of cytokine receptors and cytokine production, and via induction of acute phase proteins. Moreover, in subacute and chronic infections interleukin-1 interferes with microbial outgrowth, via mechanisms that have only been partially elucidated.
 ...
PMID:Interleukin-1 and related pro-inflammatory cytokines in the treatment of bacterial infections in neutropenic and non-neutropenic animals. 786 47

Human neutrophil azurophilic granules contain an approximately 55-kDa protein, known as bactericidal/permeability-increasing protein (BPI), which possesses a high-affinity binding domain for the lipid A component of lipopolysaccharide (LPS). The in vivo LPS neutralizing activity of exogenous BPI was studied in a model of lethal Escherichia coli bacteremia. Five baboons were treated with BPI (5 mg/kg bolus injection followed by a 95 micrograms/kg/min BPI infusion over 4 hr), while four additional animals received a genetically engineered variant of BPI (NCY103). Five animals received a placebo treatment and served as controls. Both wild-type rhBPI and NCY103 significantly (P < 0.05) decreased blood levels of LPS throughout an 8-hr evaluation period following live bacterial challenge. Two hours following E. coli administration, LPS levels peaked in the controls, at 6.86 +/- 3.22 ng/ml, whereas LPS levels were 3.39 +/- 2.1 ng/ml in the BPI group and 2.04 +/- 1.18 ng/ml in the NCY103 group. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 levels likewise were attenuated in the treatment groups, whereas circulating sTNFR I was significantly (P < 0.05) reduced only in the BPI group. Leukocytopenia and granulocytopenia were significantly (P < 0.02) lessened in the BPI group, by an average of 59% leukocytopenia and 65% granulocytopenia, respectively. This study supports the concept of E. coli LPS neutralization by BPI in vivo and demonstrates that a moderate (70%) reduction in peak LPS-LAL activity is sufficient to alter some hematologic and cytokine manifestations of bacteremia.
 ...
PMID:The role of bactericidal/permeability-increasing protein in the treatment of primate bacteremia and septic shock. 819 14

A 82-year-old woman was admitted because of dehydration and chronic renal failure. Although her renal function was improved by hydration, granulocytopenia (granulocyte number 645/mm3) occurred. Treatment with a relatively high dose of H2 blocker for one month before admission may have caused the granulocytopenia. To prevent possible infection in the patient, we administered 75 g of granulocyte-colony stimulating factor (G-CSF) for 5 consecutive days but 4 days after commencement of administration of G-CSF, pain in both knee joints suddenly appeared. Synovial fluid aspiration revealed granulocytosis (10,400/mm3) and deposition of calcium pyrophosphate dihydrate in the knee joints. The level of G-CSF in the synovial fluid was increased in the joints (700 pg/ml), compared with the serum concentration (62 pg/ml). Furthermore, the concentrations of interleukin-6 and interleukin-8 were markedly increased in the synovial fluid. The results indicated that her pseudogout exacerbation by G-CSF was at least in part explained by the increased production of cytokines in the knee joints. Because the prevalence of pseudogout and gout is overwhelming in the elderly, the possibility of GCSF induced exacerbation of joint pain should be carefully considered in elderly patients.
 ...
PMID:[An elderly case with pseudogout exacerbated by the administration of granulocyte-colony stimulating factor during drug-induced granulocytopenia]. 1055 66

A 52-year-old male with coronary artery disease was admitted with acute aortic valve endocarditis and a temperature up to 39.5 degrees C caused by Staphylococcus aureus. The patient was treated with ticlopidine (Tiklyd) after percutaneous transluminal coronary angioplasties to reduce restenosis by inhibiting thrombocyte aggregation. Upon admission c-reactive protein (CRP) was 389 mg/l. Interleukin-6 (IL-6) and Interleukin-2-receptor (IL-2-rec) were distinctly increased. Monoclonal antimyocardial antibodies were found. Leukocyte count never exceeded 9.8 G/l; however, transesophageal echocardiography validated a soft vegetation of the aortic valve. Antibiotic therapy was initiated with imipenem, gentamicin and vancomycin; clarithromycin was added after five days. Temperature normalized after 24 days. The c-reactive protein decreased from 389 mg/l to 6 mg/l, and the elevated cytokine levels decreased accordingly. Agranulocytosis or pancytopenia by ticlopidine through a toxic mechanism have been described, which are normally reversible within three weeks; there has not yet been a description of a missing leukocyte response in endocarditis as in this case report. This is a special situation with lack of or impeded immunological response, which limits the use of ticlopidine, especially since a therapeutic alternative with clopidogrel is available.
 ...
PMID:[Impediment of cellular immune response under treatment with ticlopidine in a patient with Staphylococcus aureus endocarditis]. 1101 74

Interleukin-6 (IL-6), a potent myeloid mitogen, and the immunosuppressive prostanoid prostaglandin E2 (PGE2) are elevated following thermal injury and sepsis. We have previously demonstrated that bone marrow myeloid commitment shifts toward monocytopoiesis and away from granulocytopoiesis during thermal injury and sepsis and that PGE2 plays a central role in this alteration. Here we investigated whether PGE2 can modulate IL-6-stimulated growth in the promyelocytic cell line, NFS-60, by down-regulating IL-6 receptor (IL-6r) expression. Exposure of NFS-60 cells to PGE2 suppressed IL-6-stimulated proliferation as well as IL-6r expression. Receptor down-regulation is functionally significant since IL-6-induced signal transduction through activators of transcription (STAT)-3 is also decreased. Down-regulation of IL-6r correlated with the ability of PGE2 to arrest cells in the G0/G1 phase of the cell cycle. PGE2 appears to signal through EP2 receptors. Butaprost (EP2 agonist) but not sulprostone (EP3 agonist) inhibited IL-6-stimulated proliferation. In addition, an EP2 antagonist (AH6809) alleviated the anti-proliferative effects of PGE2. NFS-60 cells express predominantly EP2 and EP4 receptors. While PGE2 down-regulated both the IL-6r protein and mRNA expression, it had no influence on EP2 or EP4 mRNA expression. The present study demonstrates that PGE2 is a potent down-regulator of IL-6r expression and thus may provide a mechanistic explanation for the granulocytopenia seen in thermal injury and sepsis.
 ...
PMID:Prostaglandin E2 mediates growth arrest in NFS-60 cells by down-regulating interleukin-6 receptor expression. 1242 18