SERUM LEVELS OF SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTORS IN PATIENTS WITH BENIGN AND MALIGNANT HPV-ASSOCIATED ANOGENITAL LESIONS

The levels of type-I and type-II soluble TNF-alpha receptors (sTNF-Rs) were evaluated in sera from patients with various human-papillomaviru s-(HPV)-associated benign and malignant anogenital lesions using speci fic enzyme-linked immunobiological assays, In patients with benign HPV 6/I I-associated condylomata acuminata, the levels of sTNF-RI were sig nificantly increased, while sTNF-RII were in normal range, Both types of sTNF-Rs were in normal range in patients with benign HPV16-associat ed grade-I/II and grade-III cervical intra-epithelial neoplasia, Howev er, their levels were significantly increased in patients with HPV16/1 8-associated squamous cervical cancer and anogenital Bowen's carcinoma . Sera from patients with condylomata acuminata and anogenital carcino mas displayed significantly increased TNF-alpha-inhibitory activity, a s revealed by L929 cell-cytotoxicity assay, Increased serum TNF-alpha- inhibitory activity correlated with higher levels of sTNF-Rs, Furtherm ore, this inhibitory activity could be specifically abrogated by htr9 and utr1 monoclonal antibodies recognizing TNF-RI and TNF-RII respecti vely, Our results strongly suggest that serum sTNF-Rs may protect tumo r cells from cytotoxic/cytostatic effects of locally released TNF-alph a, and that elevated levels of circulating sTNF-Rs may facilitate the growth of HPV-associated anogenital lesions. (C) 1997 Wiley-Liss, Inc.