osteoprotegerin and Neutropenia

The purpose of this study is to determine the levels of procalcitonin (PCT), IL-8 (interleukin-8), MIF (macrophage migration inhibitory factor), osteoprotegerin (OPG), hs-CRP and D-dimer during fever above 38.3°C due to various causes.. Blood samples taken from a total of consecutive 65 hospitalized patients during fever were prospectively tested for hsCRP, PCT, IL-8, OPG, MIF and D-dimer. Of these patients, there were 26 patients presenting with chemotherapy-induced neutropenia who had no infectious agents found; 23 patients, who had a malignancy with a febrile episode which was neither a microbiologically documented infection nor a chemotherapy-induced neutropenia, and 16 patients who did not have a malignancy and were considered to have a clinically and microbiologically documented infection.. IL-8 and D-dimer levels were higher in patients with febrile neutropenia than in the other two groups. Although MIF and OPG were higher in patients with newly diagnosed cancers, there were no differences among the three groups regarding PCT and hs-CRP values.. High serum IL-8 and D-dimer levels can be useful markers to identify hospitalized chemotherapy-induced neutropenia patients. MIF and OPG were found to be higher in patients with newly diagnosed cancer.

Topics: Antineoplastic Agents; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Fibrin Fibrinogen Degradation Products; Humans; Infections; Interleukin-8; Intramolecular Oxidoreductases; Macrophage Migration-Inhibitory Factors; Male; Neoplasms; Neutropenia; Osteoprotegerin; Prospective Studies; Protein Precursors

Gfi1 is a key molecule in hematopoietic lineage development and mutations in GFI1 cause severe congenital neutropenia (SCN). Neutropenia is associated with low bone mass, but the underlying mechanisms are poorly characterized. Using Gfi1 knock-out mice (Gfi1-ko/ko) as SCN model, we studied the relationship between neutropenia and bone mass upon different pathogen load conditions. Our analysis reveals that Gfi1-ko/ko mice kept under strict specific pathogen free (SPF) conditions demonstrate normal bone mass and survival. However, Gfi1-ko/ko mice with early (nonSPF) or late (SPF+nonSPF) pathogen exposure develop low bone mass. Gfi1-ko/ko mice demonstrate a striking rise of systemic inflammatory markers according to elevated pathogen exposure and reduced bone mass. Elevated inflammatory cytokines include for instance Il-1b, Il-6, and Tnf-alpha that regulate osteoclast development. We conclude that low bone mass, due to low neutrophil counts, is caused by the degree of systemic inflammation promoting osteoclastogenesis.

Topics: Animals; Body Weight; Bone and Bones; Cell Differentiation; Congenital Bone Marrow Failure Syndromes; Cytokines; DNA-Binding Proteins; Extremities; Genotype; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neutropenia; Osteoblasts; Osteogenesis; Osteoporosis; Osteoprotegerin; Pasteurellaceae; RANK Ligand; Transcription Factors; Trichomonas

A new entity manifested by severe congenital neutropenia associated with osteoporosis and recurrent bone fracture is described in a family. A possible role for a new recognized cytokine system involved in bone remodeling, the osteoprotegerin/receptor activator of nuclear factor-kappa B ligand, is suggested.

Topics: Agammaglobulinemia; Bone Remodeling; Carrier Proteins; Cells, Cultured; Child, Preschool; Consanguinity; Failure to Thrive; Fibroblasts; Filgrastim; Fractures, Spontaneous; Genes, Recessive; Glycoproteins; Granulocyte Colony-Stimulating Factor; Humans; Immunoglobulins, Intravenous; Male; Membrane Glycoproteins; Neutropenia; Osteoporosis; Osteoprotegerin; Pancytopenia; Pedigree; Peripheral Blood Stem Cell Transplantation; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Recombinant Proteins; Recurrence