Serum values of tumour necrosis factor-alpha and of soluble tumour necrosis factor-R55 in melanoma patients

Tumour necrosis factor-alpha (TNF alpha) is a cytokine with a variety of bi ological activities, including an effect on tumour growth. The soluble TNF receptor TNF-R55 (sTNF-R55) inhibits TNF alpha functioning. Serum values of TNF alpha and TNF-R55 have been observed in patients with different cancer s. To determine the serum values of TNF alpha and its soluble receptors and to investigate the prognostic value of sTNF-R55, we studied the sera of 68 patients with metastatic melanoma, 109 patients with no recurrent disease after surgical removal of melanoma, and 69 healthy controls. At least four different monoclonal antibodies against human TNF alpha and human TNF-R55, respectively, were prepared to obtain sensitive and reliable sandwich enzym e-linked immunosorbent assays. We found that in patients with metastatic me lanoma the serum values of sTNF-R55 were significantly higher (2.41 ng/ml; range 0.02-23.0 ng/ml; P < 0.05) than in the melanoma patients without recu rrence (0.54 ng/ml; range 0.02-6.25 ng/ml) and healthy controls (0.5 ng/ml; range 0.02-5.0 ng/ml). The sTNF-R55 concentrations increased as the diseas e progressed. Patients with metastatic melanoma also had significantly high er concentrations of TNF alpha (3.34 ng/ml; range 0.03-30.0 ng/ml; P < 0.05 ) than patients without recurrence (1.24 ng/ml; range 0.02-23.0 ng/ml). Pat ients with metastatic melanoma, a high sTNF-R55 concentration, a low TNF al pha concentration and a low TNF : sTNF-R55 ratio had the worst prognosis. L ow values of sTNF-R55 (< 0.6 ng/ml) were associated with favourable respons e to chemotherapy (P = 0.007). According to our findings, patients with met astatic melanoma have higher values of sTNF-R55 than the controls and melan oma patients without recurrence. sTNF-R55 values higher than 0.6 ng/ml and a TNF:sTNF-R55 ratio lower than 1.5 are unfavourable prognostic factors for response to chemotherapy. (C) 2000 Lippincott Williams & Wilkins.