PRESENCE OF HIGH-LEVELS OF LEUKOCYTE-ASSOCIATED INTERLEUKIN-8 UPON CELL ACTIVATION AND IN PATIENTS WITH SEPSIS SYNDROME

In inflammatory and infectious diseases, the presence of circulating c ytokines in plasma strongly suggests, following their exacerbated prod uction, that saturation of specific binding sites has occurred or that an equilibrium between receptor-bound and free cytokines has been rea ched. In this report, we demonstrate that in addition to circulating i nterleukin-8 (IL-8), high levels of cell-associated IL-8 were detected in blood samples from patients with sepsis syndrome. The following an alysis will reveal that in addition to erythrocytes, which have been d ubbed a ''sink'' for IL-8, peripheral blood mononuclear cells (PBMC) a nd polymorphonuclear cells (PMN) contributed to the detection of cell- associated IL-8. On a per cell basis, 2,000 to 7,000 times the amount of IL-8 was found associated with PMN than with erythrocytes. In addit ion, circulating cells may well be the source of the leukocyte-associa ted form of IL-8. Similarly, in vitro experiments, such as whole-blood stimulation assays or the addition of exogenous IL-8 in blood samples , demonstrated that a large proportion of the IL-8 was associated with leukocytes. This suggests that the trapping of free cytokines onto th e cell surface and the internalization of the IL-8 bound to its recept or, occurring both in vitro and in vivo, allows the detection of this cell-associated form. This analysis of cell-associated cytokines was e xtended to IL-1ra, another component of the inflammatory response, whi ch, in contrast to IL-8, has been demonstrated to exist as an intracel lular form, Indeed, cell-associated IL-1ra was also detected in septic patients. The measurement of cell-associated proinflammatory and anti -inflammatory cytokines in patients is clearly a more reliable reflect ion of their production than is the simple measurement in plasma and m ay provide useful indication to further understand the inflammatory pr ocess.