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Increased Synovial Interleukin-8 and Interleukin-6 Levels in Pseudogout Associated with Granulocyte Colony-Stimulating Factor
- Shinji Teramoto, MD;
- Hiroshi Yamamoto, MD; and
- Yasuyoshi Ouchi, MD
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TO THE EDITOR:
Although granulocyte colony-stimulating factor (GCSF) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy, several side effects, including bone pain, were noted in patients given GCSF [1]. Furthermore, Sandor and colleagues [2] recently suggested that pseudogout can be caused by GCSF. Because GCSF can provoke the other proinflammatory cytokines, GCSF-induced cytokines may affect pseudogout in joints. However, no evidence is available on the direct involvement of GCSF-related cytokines in pseudogout. We report a case of pseudogout after GCSF treatment in which synovial levels of GCSF, interleukin (IL)-8, and IL-6 were markedly increased.
An 83-year-old woman was admitted to the hospital with granulocytopenia (granulocyte count, 960 cells/mm3) and chronic renal failure. We administered GCSF to prevent possible infection. After 5 consecutive days of subcutaneous administration of 75 µg of GCSF, pain in both knee joints suddenly developed. The patient had no history of any joint pain. Radiographs of the knee joints showed chondrocalcinosis. Approximately 50 mL of synovial fluid was aspirated from each knee joint. Although the blood granulocytes count was normal (2060 cells/mm3), granulocytosis (granulocyte count, 10 400/mm3) and calcium pyrophosphate dihydrate were identified in synovial fluid. These findings indicated that the joint pain was pseudogout. The synovial GCSF level was increased in both knee joints (700 pg/mL). Very high levels of IL-6 (118 000 pg/mL) and IL-8 (8180 pg/mL) and normal levels of tumor necrosis factor-α and IL-1 β were also seen in synovial fluid. In contrast, serum levels of GCSF (62 and 12 pg/mL), IL-6 (76.8 and 20.3 pg/mL), and IL-8 (<12.5 pg/mL) were not markedly increased during pseudogout or the recovery period, respectively.
It has been suggested that IL-8 is the major neutrophil chemotaxin in synovial fluid in pseudogout [3]. Experimental data also revealed that IL-8 production induced by granulocyte-macrophage colony-stimulating factor was synergistically enhanced in the presence of a crystal (calcium pyrophosphate dihydrate) [4]. Taken together, the pseudogout exacerbated by GCSF was at least partly explained by the increased production of cytokines in the knee joints. Thus, patients with crystal-induced synovitis (pseudogout) may be at risk for the exacerbation of insidious inflammation of joints after GCSF administration.
Shinji Teramoto, MD
Hiroshi Yamamoto, MD
Yasuyoshi Ouchi, MD
Tokyo University Hospital; Tokyo, 113 Japan
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
