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The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), alpha 1-antitrypsin (ATT), alpha 1-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx (n = 9), oral cavity (n = 4), oropharynx (n = 3) and hypopharynx (n = 2). Proteins were measured at three time points before and three time points after surgery. Significant (P < 0.0001) relationships were found between IL-6 and CRP (r = 0.69), and fibrinogen (r = 0.51), whereas no correlation was found with AAT (r = 0.13, P = 0.56), AAG (r = 0.38; P = 0.07) and HPT (r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies.

Forty-five consecutive cases of nasopharyngeal carcinoma were morphologically and immunocytochemically studied using monoclonal (anti-B and anti-T cell) and polyclonal (anti-S100 protein and antilysozyme) antibodies with the peroxidase-anti-peroxidase method to identify infiltrating lymphocytes (T and B cell) and histiocytes (monocytic/macrophagic and dendritic cells) in nasopharyngeal carcinoma. A variable density of dendritic cells was found within the tumor nests in 22 (49%) of 45 nasopharyngeal carcinomas examined; infiltrating macrophages were demonstrated in 15 (33%) specimens and around the tumor in almost all cases. Cases with moderate or marked density of dendritic cells (S100+) survived longer than those without such infiltration (mean 5-year survival rates of 31%, 55%, or 64% in patients with absent, moderate, or marked densities, respectively; P less than 0.05). A significant relationship between monocytic/macrophagic cells (lysozyme+) within the tumor and survival was also found (mean 5-year survival rate of 27% or 61% in patients with absent, moderate, or marked densities, respectively). However, lymphocytic infiltration was not statistically related to a better survival. Analyzing lymphocytic infiltration, we found a large prevalence of T cells in the neoplastic tissue without any prognostic significance. These data were correlated to different histological subtypes according to the principal histological classifications of nasopharyngeal carcinomas (Micheau, et al.; World Health Organization; Cologne University) to individualize the scheme which correlates best with prognosis and biological features of nasopharyngeal carcinomas. Our data suggest that, considering dendritic cells and macrophages within cancer nests, nasopharyngeal carcinoma histiotypes can be correlated to patient prognosis.

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Summary In patients with advanced head and neck squamous cell carcinoma (HNSC), evidence of cellmediated immunity and monocyte functional abnormalities has been reported. We studied the production of interleukin 1 beta (IL-lbeta) and interleukin 6 (IL-6) by peripheral blood monocytes from 22 patients with HNSC (12 larynx and ten oral cavity cancers) in comparison with monocyte cytokine production of age-matched healthy subjects. Pure monocytes were incubated with and without lipopolysaccarides (LPS) (10 1tg ml-') for 4 h at 37C and IL-Ibeta and IL-6 concentrations were determined in supernatants by specific ELISA. There was no significant difference in IL-1beta levels in monocyte supernatants from cancer in comparison to control subjects; conversely, a higher IL-6 production by unstimulated and LPS-activated cells from HNSC patients than from controls was found. No relationship was observed between cytokine production and cancer stage. The regression analysis evidenced a significant correlation between IL-lbeta and IL-6 monocyte-release in HNSC patients and in controls, so suggesting a possible autocrine control of IL-6 production by other cytokines.