Elevation of circulating plasma cytokines in cancer patients with high plasma parathyroid hormone-related protein levels.
Parathyroid hormone (PTH) and PTH-related protein/peptide (PTHrP) bind to the same PTH/PTHrP receptor and stimulate osteoblasts to secrete pro-inflammatory cytokines like interleukin (IL)-6. In patients with primary hyperparathyroidism, elevation of plasma levels of tumor necrosis factor (TNF)-alpha and IL-6 was also described. We, therefore, postulated that PTHrP secreted from cancer cells stimulates the secretion of cytokines and causes increases in their blood levels. Blood concentrations of several cytokines (TNF-alpha, IL-1beta, IL-5, IL-6, IL-8, IL-11 and IL-12) in cancer-bearing patients with or without elevation of blood PTHrP were measured by ELISA. The patients with high plasma PTHrP levels (n=29, intact PTHrP: 8.5 +/- 1.4 pmol/l, normal: <1.1) had higher serum type 1 collagen C-telopeptide (ICTP). Twenty of the patients were hypercalcemic. Plasma concentrations of TNF-alpha, IL-6 and IL-8 were significantly increased in patients with high PTHrP, in either the presence or absence of hypercalcemia. The concentrations of TNF-alpha and IL-6 were also significantly correlated with those of PTHrP. Our observations indicate that high plasma levels of PTHrP in cancer-bearing patients contribute not only to the development of hypercalcemia, but also to the development of the syndrome caused by an excess of pro-inflammatory cytokines.
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000097:blood / Q000473:pathology / Q000556:secondary; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000473:pathology; D044162:Parathyroid Hormone-Related Protein / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood
D014408:Biomarkers, Tumor; D024042:Collagen Type I; D016207:Cytokines; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen