CYTOKINE PRODUCTION BY MONONUCLEAR-CELLS FOLLOWING STIMULATION WITH APEPTIDE-CONTAINING, ENDOTOXIN-FREE ESCHERICHIA-COLI EXTRACT

The beneficial effects of the E. coli extract Colibiogen(R) inj. N (Cb ) observed in therapy of inflammatory bowel diseases, allergies, ol ga strointestinal turners are possibly mediated by the indiction of cytok ines in human leukocytes or vascular cells. Thus, the induction of the cytokines interleukin 1 (IL1), IL6 and tumor necrosis factor (TNF) in human mononuclear cells (MNC) and vascular cells was investigated in vitro. Various administration forms of the extract (including Cb-inj. N Cb-oral, and Cb-infantibus N) induced the release of IL1 and IL6 fro m MNC. The compounds stimulated TNF production less potently, possibly due to a lower sensitivity of the TNF assay system, as compared to th e IL1 and IL6 detection system. The MNC produced the cytokines with a kinetics similar to that observed with other stimuli. Monospecific ant ibodies abolished the respective cytokine activity in the biological a ssays. Addition of submaximal amounts of endo toxin po tent ly enhance d the IL1- and IL6-inducing activity of the bacterial extract, indicat ing synergism of the extract and endotoxin. These results provide evid ence that cytokines produced by MNC following administration of the te sted bacterial extract may contribute to the regulation of the immune response during therapy of gastrointestinal tumors. At present the in vivo production of cytokines following treatment with the bacterial ex tract tested is under investigation in a phase III study.