CAPSULAR POLYSACCHARIDE OF CRYPTOCOCCUS-NEOFORMANS INDUCES PROINFLAMMATORY CYTOKINE RELEASE BY HUMAN NEUTROPHILS

Human polymorphonuclear leukocytes from normal subjects produced proin flammatory cytokines in response to stimulation with Cryptococcus neof ormans yeast cells. The cytokines released after stimulation of neutro phils included interleukin-1 beta (IL-1 beta), IL-6, IL-8, and tumor n ecrosis factor alpha. The magnitude of the cytokine response was relat ed to the yeast capsule size. Cells of a large-capsule isolate stimula ted release of greater amounts of cytokine than did a thinly encapsula ted isolate, which, in turn, stimulated release of greater amounts of cytokine than an acapsular isolate. Cytokine release was also stimulat ed by supernatant fluids from cryptococcal cells that were preincubate d with 10% human serum, suggesting the generation of a soluble mediato r. The major capsular polysaccharide, glucuronoxylomannan, stimulated release of tumor necrosis factor alpha, IL-1 beta, and IL-8 in a dose- dependent fashion. These results differ from previous studies of cytok ine secretion by human monocytes in several important respects, includ ing the importance of encapsulation in stimulation of cytokine secreti on and the ability of purified glucuronoxylomannan to induce cytokine secretion.