Role of interleukin-6 in paraneoplastic thrombocytosis [letter]

Abstract

Interleukin-6 (IL6) is able to stimulate thrombopoiesis in vitro and in vivo in murine and primate models.',' A phase I trial of recombinant IL-6 in humans has demonstrated the capacity of this cytokine for increasing platelet counts in vivo.' However, the physiologic role of IL-6 in the regulation of thrombopoiesis remains unclear." Increased serum IL-6 levels have been reported in patients with reactive thrombocytosis but the causative role of IL-6 for thrombocytosis has not been e~tablished.~ We report here on the role of IL-6 in paraneoplastic thrombocytosis associated with metastatic renal carcinoma. We previously showed that serum IL-6 is increased in a subgroup of patients with renal cell carcinoma.6 The possible correlation between serum IL-6 measured with the B9 bioassay and thrombocyte counts was investigated in a series of I00 patients with metastatic renal cell carcinoma. The 26 patients with undetectable serum IL-6 had a mean platelet number of 3.12 X 105/pL compared with 3.62 X 105/pL in the 5 1 patients with detectable serum IL-6 less than 10 U/mL (Mann-Whitney, P = .04) and 4.72 X 105/pL for the 23 patients with serum IL-6 greater than 10 U/mL (P = .001). CORRESPONDENCE able to normalize thrombocytosis in patients with metastatic renal carcinoma. This demonstrates that an overproduction of IL-6 in vivo is responsible for the paraneoplastic thrombocytosis associated with renal cell carcinoma.

Poor Prognosis Associated With Thrombocytosis in Patients With Renal Cell Carcinoma

“…Secondary or reactive thrombocytosis occurs in several clinical conditions, including various malignancies [4]; it also occurs in patients with metastatic RCC [5]. We observed that some patients with thrombocytosis and metastatic RCC had a shorter life expectancy than those with a normal platelet count.…”

“…They noted a 65% 5-year survival rate in patients with a normal platelet count, whereas those patients with thrombocytosis had a 5-year survival rate of only 25%. Only recently have Blay et al [5] noted thrombocytosis associated with metastatic RCC in their studies of IL-6.…”

Elevated platelet count in patients with endometrial carcinoma: correlation with selected prognostic factors and with survival

“…It has been shown that cytokines produced by malignant cells, such as interleukin-6 and colony stimulating factors (17)(18)(19), are associated with thrombocytosis. These cytokines are also produced by ovarian cancer (17'2°-22).…”

Impact of thrombocytosis and C‐reactive protein elevation on the prognosis for patients with renal cell carcinoma

“…10 The reactive THC and CRP elevation in RCC are both caused by the production of inflammatory cytokines such as IL-6. [11][12][13] When metastatic RCC is treated with IL-2, serum IL-6 levels and CRP levels are correlated and the survival of patients with detectable IL-6 is shorter than that of patients with undetectable IL-6. 14 RCC patients with elevated serum IL-6 frequently have higher platelet counts and higher CRP levels than do those without elevated IL-6, 12 and elevated serum IL-6 elevation is also significantly associated with paraneoplastic THC in patients with RCC.…”