Disease relevance of IL-6

• These data support the hypothesis that cytokines such as IL-6 are important amplification molecules for CNS inflammation in Lyme neuroborreliosis [1].
• However, among rapid progressors, the eight animals with SIV encephalitis had a unique cytokine profile (increased IL-2, IL-6, and IFN-gamma) that was associated with higher viral loads [2].
• Recall responses to rotavirus by CD4(+) and CD8(+) T lymphocytes were associated with accumulation of intracellular IL-6 and gamma interferon [3].
• Following intravenous inoculation of pig-tailed macaques with SIV-PBj14, acute disease developed and was characterized by high levels of plasma viremia, p27gag antigenemia, tumor necrosis factor alpha, and interleukin-6 (IL-6) [4].
• Rhesus monkeys were treated s.c. with recombinant human (rh) IL-6 at 3 and 30 micrograms/kg body weight/day for 11 days, followed by the administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) at 5.5 micrograms/kg/day for 5 days [5].

Psychiatry related information on IL-6

• The large release of IL-6 into CSF suggests that some behavioral symptoms may be due to intrinsic changes in central nervous system activity concomitant with the alterations in peripheral physiology [6].
• There is also speculation that IL-6 may contribute to the pathogenesis of several diseases that are common in late-life including lymphoma, osteoporosis, and Alzheimer's disease [7].

High impact information on IL-6

• A large fraction (> 30%) of single-cell/well-sorted CD34bright/RhLA-DRdull cells formed multilineage colonies after 2 to 4 weeks of stimulation with IL-3, GM-CSF, Kit ligand, and IL-6 [8].
• We conclude that IL-6 significantly alters the process of megakaryocyte maturation and thrombocytopoiesis, and that these effects, at least in the doses of IL-6 administered, should not be equated with the physiologic mechanisms operative during accelerated platelet production [9].
• Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in mice and primates [9].
• Cytokine gene expression (interleukin-1beta [IL-1beta], IL-2, IL-6, IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and viral loads were evaluated by semiquantitative reverse transcription-PCR in lymph nodes of 5 control animals and 28 animals infected with SIVmac251 at the terminal stages of AIDS [2].
• Elevated levels of IL-6 cDNA and, to a lesser extent, interferon gamma were detected in three of three nonhuman primates with persistent infection with B burgdorferi, whereas the brains of three uninfected animals and undetectable levels of gene expression of these cytokines [1].

Biological context of IL-6

• In humans and nonhuman primates, the in vivo administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) consistently results in marked increase of megakaryocyte ploidy and size similar to that observed with interleukin-6 (IL-6) [10].
• Cerebrospinal fluid (CSF) and blood levels of interleukin-6 (IL-6) were measured, as well as cortisol levels and body temperature [11].
• In the present study, the likely involvement of inflammatory cytokines, namely, leukemia inhibitory factor (LIF), interleukins 1 alpha and 1 beta (IL-1alpha and IL-1beta) and IL-6 at the primary implantation site of the rhesus monkey was examined immunocytochemically during lacunar (n=6) and villous (n=8) stages of gestation [12].
• The Tibetan macaque IFN-gamma and IL-6 cDNAs were found to be 498 and 639bp in length, with open reading frames encoding 165 and 212 amino acids, respectively [13].
• Homology analyses indicated that the identity levels of nucleotide and deduced amino acid sequences of IFN-gamma among primates ranged from 93.4 to 99.2%, and 87.3 to 99.4%, respectively, and that of IL-6 ranged from 92.6 to 99.8%, and 85.4 to 99.5%, respectively [13].

Anatomical context of IL-6

• To elucidate the mechanisms underlying this phenomenon, serial analyses were performed on megakaryocytes obtained from rhesus monkeys treated for 8 days with 30 micrograms/kg/d of recombinant human IL-6 [9].
• Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand [14].
• IL-6 production was not observed when control cell lines were stimulated in the same fashion [15].
• Therefore, gene expression for the monocyte/macrophage-derived cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha was determined before and during H. pylori infection of rhesus monkeys by use of a highly sensitive quantitative reverse transcriptase polymerase chain reaction [16].
• Recombinant human IL-6 treatment induced a two to threefold rise in myeloid progenitor blood cell levels [5].

Associations of IL-6 with chemical compounds

• Tumor necrosis factor alpha, IL-2, and IL-6 were detected in some cultures infected with SIV-PBj14, but this finding was not consistent [4].
• We evaluated IL-10 and IL-6 protein and gene expression after exposure to LPS and IFN-gamma protein and gene expression after PHA stimulation [17].
• Luminal and glandular epithelial cells were immunopositive for LIF, IL-1alpha, IL-1beta and IL-6 in lacunar and in villous stage samples [12].
• Total and HDL cholesterol levels fell by 16 and 23%, respectively, after IL-6 injections [18].

Other interactions of IL-6

• For both SIVmac239 and its nef-deleted derivative, strong expression was observed as early as 7 days postinfection for interleukin 1beta (IL-1beta), IL-6, tumor necrosis factor alpha, gamma interferon, and IL-13 [19].

Analytical, diagnostic and therapeutic context of IL-6

• Samples of brain tissue were screened for IL-6 and interferon gamma using RT-PCR-ELISA, a technique that uses RT-PCR, subsequent hybridization of the PCR product with a biotinylated probe, and capture and ELISA readout of hybridization product [1].
• Human interleukin 6 (IL-6) produced by molecular cloning was administered to nonhuman primates to assess its biological activities in vivo [5].
• The marked increase in IL-6 and IL-6 mRNA correlated with the virus levels in the tissues and serum as determined by viral isolation, immunohistochemistry, and Northern blot analysis [20].
• The cloning and sequence analysis of Tibetan macaque IFN-(gamma) and the IL-6 cDNAs are described [13].
• To test the effects of the chronic administration of interleukin-6 (IL-6) on lipoprotein levels in middle-aged and old rhesus monkeys, five middle-aged and five old rhesus monkeys received a subcutaneous injection of recombinant human IL-6 (15 micrograms/kg) for 28 days [18].

References