Horm Metab Res 2009; 41(4): 333-338
DOI: 10.1055/s-0028-1103300
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Overexpression of Protein Kinase C-δ Plays a Crucial Role in Interleukin-6-Producing Pheochromocytoma Presenting with Acute Inflammatory Syndrome: A Case Report

H. Tokuda 1 , 2 , T. Hosoi 3 , K. Hayasaka 4 , K. Okamura 5 , N. Yoshimi 6 , O. Kozawa 2
  • 1Department of Clinical Laboratory, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu Aichi, Japan
  • 2Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Japan
  • 3Department of Advanced Medicine, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu Aichi, Japan
  • 4Department of Clinical Radiology and National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu Aichi, Japan
  • 5Department of Intensive Care, National Hospital for Geriatric Medicine, National Center for Geriatrics and Gerontology, Obu Aichi, Japan
  • 6Tumor Pathology, University of the Ryukyus Faculty of Medicine, Okinawa, Japan
Further Information

Publication History

received 04.07.2008

accepted 03.11.2008

Publication Date:
01 December 2008 (online)

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-TXB2, a stable metabolite of thromboxane A2 (TXA2), 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-δ (PKC-δ), 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-δ 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-δ, resulting in an excess of arachidonate derivatives such as prostaglandins.

References

Correspondence

H. Tokuda

Department of Clinical Laboratory

National Hospital for Geriatric Medicine

National Center for Geriatrics and Gerontology

Obu Aichi 474-8511

Japan

Phone: +81/562/46 23 11

Fax: +81/562/46 83 96

Email: [email protected]