Overexpression of protein kinase C-delta plays a crucial role in interleukin-6-producing pheochromocytoma presenting with acute inflammatory syndrome: a case report

• Published in: Hormone and metabolic research Vol. 41; no. 4; p. 333
• Main Authors: Tokuda, H, Hosoi, T, Hayasaka, K, Okamura, K, Yoshimi, N, Kozawa, O
• Format: Journal Article
• Language: English
• Published: Germany 01.04.2009
• Subjects: Aged; Female; Gene Expression; Humans; Interleukin-6 - blood; Interleukin-6 - immunology; Pheochromocytoma - blood; Pheochromocytoma - genetics; Pheochromocytoma - immunology; Pheochromocytoma - surgery; Protein Kinase C-delta - genetics; Protein Kinase C-delta - immunology; Tumor Cells, Cultured
• ISSN: 1439-4286
• DOI: 10.1055/s-0028-1103300

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.