title: Overexpression of protein kinase C-delta plays a crucial role in interleukin-6-producing pheochromocytoma presenting with acute inflammatory syndrome: a case report.
abstract: Pheochromocytomas are tumors that may produce a variety of substances in addition to catecholamines. To date, among several cases of systemic inflammatory syndrome associated with interleukin-6 (IL-6) secretion, IL-6-producing pheochromocytomas, have been reported. However, the mechanism underlying IL-6 oversecretion in these cases has not yet been clarified. This report describes a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs including C-reactive protein elevation. The inflammatory symptoms were easily controlled by the administration of loxoprofen, a nonsteroidal anti-inflammatory drug. The plasma concentration of IL-6 and 11-d-TXB(2), a stable metabolite of thromboxane A(2) (TXA(2)), were significantly elevated in parallel with an elevation of norepinephrine in the samples obtained by selective venous sampling. A left adrenalectomy was performed, and the acute inflammatory symptoms naturally diminished without loxoprofen. Cultured tumor cells obtained from the resected specimen spontaneously released IL-6, and indomethacin inhibited the IL-6 release. According to a cDNA microarray analysis, mRNA of protein kinase C-delta (PKC-delta), prostaglandin D synthase, and arachidonate release-relating enzymes were significantly overexpressed in the tumor tissue in comparison to the adjacent nontumor tissue. The constitutive phosphorylation of PKC-delta was observed in the tumor tissue. These results strongly suggest that the systemic inflammatory syndrome in IL-6-producing pheochromocytoma, at least in part, is caused by the overexpression of PKC-delta, resulting in an excess of arachidonate derivatives such as prostaglandins.
authors.affiliation: Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu Aichi, Japan. tokuda@ncgg.go.jp
authors.forename: H
authors.initials: H
authors.lastname: Tokuda
authors.forename: T
authors.initials: T
authors.lastname: Hosoi
authors.forename: K
authors.initials: K
authors.lastname: Hayasaka
authors.forename: K
authors.initials: K
authors.lastname: Okamura
authors.forename: N
authors.initials: N
authors.lastname: Yoshimi
authors.forename: O
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000368:Aged; D005260:Female; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology; D010673:Pheochromocytoma / Q000097:blood / Q000235:genetics* / Q000276:immunology* / Q000601:surgery; D051745:Protein Kinase C-delta / Q000235:genetics* / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D015850:Interleukin-6; D051745:Protein Kinase C-delta