Ultrafiltration to reject human interleukin-1-inducing substances derived from bacterial cultures

Abstract

Interleukin-1 (IL-1), a polypeptide cytokine, is an important mediator of host responses to infection and injury. Picogram per milliliter concentrations of bacterial products (endo- or exotoxins) stimulate human monocytes to produce IL-1 in vitro. The design of this study was based on the clinical model of bacterial contamination of fluid intended to be directly injected into humans. Physiologic saline contaminated with bacterial toxins was passed through a hollow fiber ultrafilter, and the ultrafiltrates were tested for their ability to induce human IL-1 production. The ultrafiltrates were added directly to freshly obtained human blood mononuclear cells, and after 24 h of incubation the supernatant media were assayed for the presence of IL-1. The results indicate that (i) the IL-1-inducing material(s) present in bacterial cultures of gram-negative organisms is rejected by a factor of 100 to 100,000 by molecular size exclusion and by absorption; (ii) rejection is sustained for at least 32 liters of fluid; (iii) the rejection of Limulus-reactive material by the ultrafilter is greater for purified endotoxin than for native endotoxins derived from live bacterial cultures; and (iv) nonendotoxin IL-1-inducing toxins (molecular weight, 24,000) from Staphylococcus aureus are not rejected or absorbed. These results demonstrate that there is a considerable margin of safety with the ultrafiltration method and that it can be applied to clinical situations.