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 effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on cytokine profile was evaluated in a case of severe congenital neutropenia. The plasma levels of cytokines were measured before and during rhG-CSF therapy. These included G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha, interleukin-1 beta, interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4, interleukin-6 (IL-6), and tumor necrosis factor-alpha. Soluble interleukin-2 receptor (sIL-2R) was measured serially during rhG-CSF therapy. Lymphocyte subpopulations including CD2, CD3, CD4, CD8, CD19, CD20, and CD25 were also measured, rhG-CSF was administered once daily as a 30-min infusion. The patient was treated with increasing dose levels of 100, 200, 400, 800, and 1,600 micrograms/m2/day. The level of endogenous G-CSF was elevated to 334 pg/ml before treatment and GM-CSF, IL-2, IL-3, and IL-6 were slightly elevated. Clinically, he showed a moderate response to a high dose of rhG-CSF (1,600 micrograms/m2/day). Plasma levels of G-CSF markedly increased during therapy but plasma levels of other cytokines did not show significant changes during therapy and lymphocyte subpopulations did not significantly change. A drastic increase in sIL-2R expression was observed after rhG-CSF infusion and an increase in sIL-2R expression occurred even before a major increase in granulocyte counts. These results showed that a high dose rhG-CSF therapy may influence the cytokine network as judged by the increased sIL-2R expression.
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PMID:Cytokine profile during high-dose rhG-CSF therapy in severe congenital neutropenia. 750 1

Congenital neutropenia (Kostmann's syndrome [KS]) is an autosomal recessive syndrome that is characterized by profound neutropenia, resulting in major clinical infections and death. Since the neutropenia and symptoms in KS improve in response to exogenous administration of granulocyte colony-stimulating factor (G-CSF), we studied bone marrow cytokine (G-CSF, granulocyte-macrophage CSF [GM-CSF], and interleukin-6) production under both basal and stimulated conditions. No differences in G-CSF, GM-CSF, or IL-6 gene expression were found in bone marrow stromal cells between normal controls and KS patients, and all three cytokines were detected by enzyme-linked immunosorbent assay (ELISA) in medium conditioned by bone marrow stromal cells from normal donors and patients with KS. Each KS patient tested had detectable, functional G-CSF in their own serum before exogenous G-CSF administration. Since G-CSF production appeared normal in KS patients, we then asked whether we could detect structural defects in the signaling portion of G-CSF receptor genes. Polymerase chain reaction (PCR) amplification of the G-CSF receptor transmembrane region alone, and of the transmembrane plus cytosolic portions of the receptor, yielded the size products predicted from the sequences of the normal G-CSF receptor. Single-strand conformational polymorphism (SSCP) analysis of G-CSF receptor PCR products demonstrated no variance in structural conformation between KS patients and normal subjects. These results demonstrate that bone marrow stromal cells in patients with KS secrete normal concentrations of functional G-CSF and suggest that the neutropenia in KS patients is caused by an inability of neutrophilic progenitor and precursor cells to respond to normal, physiologic levels of G-CSF. Such a defect, clinically responsive to pharmacologic doses of G-CSF, might be caused by defects in the post-G-CSF receptor signal transduction pathway.
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PMID:Granulocyte colony-stimulating factor (G-CSF) production and G-CSF receptor structure in patients with congenital neutropenia. 751 Jan 42