TNF PRODUCTION AND HLA ANTIGENS IN PATIENTS WITH SILICOSIS.
          Gerbase-DeLima M, Setta  JH, Ribeiro O G, Bagatin E.  Department of Pediatrics, Escola Paulista de Medicina, UNIFESP, São Paulo, SP, Brazil.
          Silicosis is a chronic progressive granulomatous and fibrotic lung disease caused by inhaled silica. Considering that a pivotal role of TNF has been demonstrated in silica-induced pulmonary fibrosis in mice and that the level of TNF secretion in humans has been correlated with some HLA haplotypes, the aim of this study was: (1) to evaluate the production of TNF by silicotic patients as compared to non-silicotic individuals who had been occupationally exposed to silica (exposed controls) and to non-exposed normal controls; (2) to search for an association between HLA antigens and silicosis. The silicotics and the exposed controls did not differ in terms of intensity or time of exposure to silica dust. The TNF production was determined in heparinized whole blood (1 ml) stimulated with 10 mg of lipopolysaccharide (LPS, Sigma), at 37oC, for 6 hours. The bioactive TNF was measured in the plasma by the L929 bioassay. HLA-A, B, DR and DQ antigens were determined in 50 silicotic patients and their frequencies were compared (Fisher's exact test) to those of an ethnically matched control population sample. The median TNF production by silicotic patients (n=38), exposed controls (n=39) and non-exposed controls (n=15) was 9.7, 7.7, and 2.0 ng/ml, respectively (silicotic x exposed controls: P = 0.05; exposed controls x non exposed controls: P < 0.0001). Comparison of HLA antigenic frequencies between silicotic patients and controls did not disclose any significant association. We concluded that: a) the in vivo exposure to silica is clearly associated with an increased in vitro production of TNF; b) the difference between the TNF production by the silicotic patients and by the exposed controls, albeit statistically significant, is quite small and thus of questionable biological significance; c) there is no association between HLA- A, B, DR or DQ antigens and silicosis.