DOWN-REGULATION BY CRYPTOCOCCAL POLYSACCHARIDE OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA SECRETION FROM HUMAN MONOCYTES

The regulation by Cryptococcus neoformans encapsulation of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) produc tion by human monocytes was investigated. By using encapsulated and ac apsular C. neoformans, we demonstrated that both strains induce cytoki ne production, although the acapsular strain was a better stimulator t han the thinly encapsulated strain. The cytokine levels produced by ce lls stimulated by the two strains were lower and followed a different kinetic than those stimulated by lipopolysaccharide (LPS). Purified ca psular polysaccharide inhibits TNF-alpha secretion induced by LPS or a capsular C. neoformans. In contrast, no regulatory effect on IL-1 beta was observed when LPS was used. The secretory response of these cytok ines follows different pathways of macrophage activation; in fact, com plete inhibition of TNF-alpha does not affect IL-1 beta-production and vice versa. These data indicate that purified capsular polysaccharide of C. neoformans could contribute to the in vivo progress of cryptoco ccosis by suppressing cytokine production of macrophages and suggest t hat a therapeutic approach to address the suppressive effect of crypto coccal polysaccharide could be devised.